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which makes the lung tissue the principal target for circulating oxidants and xenobiotics&#46; Asthmatic patients produce a variety of mediators&#44; including reactive oxygen species &#40;ROS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> An increase in oxidative damage can contribute to both the origin and development of respiratory diseases&#44; including bronchial asthma&#46; Lung lesions due to ROS are related with the oxidation of deoxyribonucleic acid &#40;DNA&#41;&#44; proteins and lipids&#46; These oxidized biomolecules can induce various responses and a cascade of events&#44; such as airway hyperreactivity&#44; increase in the generation of chemoattractants&#44; release of tachykinins and neurokinins&#44; and an increase in the release of mediators which ultimately aggravate the oxidative damage&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The lungs can use non-enzymatic antioxidants&#44; such as vitamins&#44; uric acid&#44; glutathione&#44; sulfhydryl groups &#40;proteins&#44; peptides and amino acids&#41; and various enzymatic antioxidants&#44; such as superoxide dismutase&#44; catalase &#40;CAT&#41; and glutathione peroxidase as a defense against oxidative damage and ROS&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">CAT &#40;EC 1&#46;11&#46;1&#46;6&#41; is a common antioxidant enzyme responsible for controlling the hydrogen peroxide concentrations in cells&#46; It is ubiquitous in most aerobic cells also detected in the lungs &#40;macrophages&#44; fibroblasts and pneumocytes&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> As an intracellular antioxidant enzyme&#44; CAT catalyses the breakdown of two hydrogen peroxide molecules into one oxygen molecule and two water molecules&#59; its activity is determined genetically&#46; The <span class="elsevierStyleItalic">CAT</span> gene is located on chromosome 11p13&#59; it is 34<span class="elsevierStyleHsp" style=""></span>kb long&#44; contains 13 exons and 12 introns and codes a 256-amino acid protein&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Various polymorphisms of this enzyme have been described and characterized&#44; both in the coding<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> and non-coding region&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;11</span></a> A common polymorphism in the <span class="elsevierStyleItalic">CAT</span> gene promoter region is the substitution of T for C in position T -262 in the 5&#8242; region&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> which is considered to lead to a decrease in enzyme activity&#46; The <span class="elsevierStyleItalic">CAT</span> TT genotype could be responsible for a reduction in the antioxidant defense and a subsequent increase in oxidative damage&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Since oxidative damage plays a role in the pathogenesis of asthma&#44; and CAT is critical for protecting cells against ROS&#44; we hypothesized that the polymorphisms in the CAT gene that influence its enzyme activity contribute substantially to the onset of the disease&#46; This study aimed to evaluate <span class="elsevierStyleItalic">CAT</span> polymorphism -262 C&#47;T in asthmatic children&#46; We sought to determine markers of oxidative damage&#44; and to analyze a possible association between the <span class="elsevierStyleItalic">CAT</span> genotype and oxidative damage of proteins and lipids in asthmatic and healthy children&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study Individuals</span><p id="par0020" class="elsevierStylePara elsevierViewall">The study population consisted of 457 children&#46; Using the categories from reference questionnaires&#44; the asthma history of the children was recorded&#58; age&#44; sex&#44; exposure to cigarette smoke and family history of asthma&#44; wheezing and allergy&#46; The children or their parents completed the Asthma control test<span class="elsevierStyleSup">&#174;</span>&#46; Active smokers and children exposed to passive smoking were then excluded from the study&#46; The 248 asthma patients &#40;58&#37; boys and 42&#37; girls&#41; were enrolled from the Pediatrics Department of Martin University Hospital &#40;Slovakia&#41;&#46; During routine health checks&#44; general practitioners recruited a further 249 healthy children of comparable age and sex &#40;54&#37; boys and 46&#37; girls&#41;&#46; The children did not present any clinical symptoms of allergic diseases and had no history of serious illness&#46; Asthmatic children who participated in the study were characterized by recurrent airway obstruction&#44; manifested by wheezing and dyspnea&#44; with spontaneous relief with bronchodilator treatment &#40;as defined in the Global Asthma Initiative&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All children underwent fractional expired nitric oxide &#40;FE<span class="elsevierStyleInf">NO</span>&#41; and expired carbon monoxide &#40;eCO&#41; analyses&#46; The FE<span class="elsevierStyleInf">NO</span> was determined according to American Thoracic Society&#47;European Respiratory Society &#40;ATS&#47;ERS&#41; standards<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> using a portable nitric oxide analyzer &#40;NIOX-MINO<span class="elsevierStyleSup">&#174;</span>&#44; Aerocrine&#44; Sweden&#41;&#46; The eCO was analyzed using a Micro 4 Smokerlyzer<span class="elsevierStyleSup">&#174;</span> &#40;Bedfont&#44; England&#41;&#46; We also carried out basic spirometry &#40;KoKo DigiDoser-Spirometer&#44; nSpire Health&#44; Louisville&#44; United States&#41;&#44; in accordance with ATS&#47;ERS recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The FE<span class="elsevierStyleInf">NO</span> and eCO values were estimated before the spirometer test&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The study was approved by the Jessenius Faculty of Medicine&#44; Martin&#44; and written informed consent was obtained from the parents of all the children examined&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Isolation of Deoxyribonucleic Acid</span><p id="par0035" class="elsevierStylePara elsevierViewall">Blood samples were extracted into ethylene-diamine-tetraacetic acid &#40;EDTA&#41; tubes&#46; The genomic DNA was prepared using blood according to a commercial procedure &#40;Wizard<span class="elsevierStyleSup">&#174;</span> Genomic DNA purification kit&#44; Promega&#44; Madison&#44; USA&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Determination of Catalase Genotypes</span><p id="par0040" class="elsevierStylePara elsevierViewall">All DNA samples from asthmatic and healthy children were genotyped by polymerase chain reaction &#40;PCR&#41;&#44; followed by restriction fragment length polymorphism &#40;RFLP&#41; analysis&#46; CAT polymorphism -262 C&#47;T &#40;rs 1001179&#41; was determined using direct primer 5&#8242;-AGAGCCTCGCCCCGCCGGACCG-3&#8242; and CAT reverse primer 5&#8242;-TAAGAGCAGAGAAAGCATAGCT-3&#8242;&#46; PCR products of 185<span class="elsevierStyleHsp" style=""></span>bp were digested using the restriction enzyme Smal&#46; The products were visualized by 2&#37; agarose gel electrophoresis&#46; The wild-type CC genotype appeared as 155 and 30<span class="elsevierStyleHsp" style=""></span>bp fragments&#44; and the CT genotype as 185&#44; 155 and 30<span class="elsevierStyleHsp" style=""></span>bp fragments&#46; TT genotypes were not digested by Smal &#40;185<span class="elsevierStyleHsp" style=""></span>bp&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Plasma Protein Sulfhydryl Groups</span><p id="par0045" class="elsevierStylePara elsevierViewall">Plasma for determination of protein and lipid markers of oxidative damage was obtained from blood prepared by centrifugation for 20<span class="elsevierStyleHsp" style=""></span>min&#44; at 2000&#215;<span class="elsevierStyleItalic">g</span> at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The total concentration of reduced sulfhydryl groups &#40;&#8722;SH&#44; proteins&#44; oligopeptides&#44; glutathione and amino acids&#41; was determined by spectrophotometry&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Two ml of Ellman&#39;s reagent &#40;0&#46;250<span class="elsevierStyleHsp" style=""></span>mol&#47;l of Tris&#8211;HCl&#59; pH 8&#46;2&#44; 10<span class="elsevierStyleHsp" style=""></span>mmol&#47;l of 5&#46;5&#8242;-dithiobis-2-nitrobenzoic acid&#41; were added to 100<span class="elsevierStyleHsp" style=""></span>&#956;l of sample and incubated for 15<span class="elsevierStyleHsp" style=""></span>min at room temperature&#46; The absorbance was read at 412<span class="elsevierStyleHsp" style=""></span>nm and &#8211;SH group content was calculated using the molar absorption coefficient of 13<span class="elsevierStyleHsp" style=""></span>600<span class="elsevierStyleHsp" style=""></span>M<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">&#8722;1</span> after subtracting the absorbance of the blank from the sample absorbance&#46; A population of 249 healthy individuals was used to determine the normal value&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Lipid Peroxide Analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Modifications in the structure of the plasma lipids were analyzed by determining the thiobarbituric acid-reactive substances &#40;TBARS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> A sample was incubated with ethanol&#44; 14&#37; trichloroacetic acid and 0&#46;6&#37; thiobarbituric acid at 80<span class="elsevierStyleHsp" style=""></span>&#176;C for 30<span class="elsevierStyleHsp" style=""></span>min&#46; It was then incubated for 5<span class="elsevierStyleHsp" style=""></span>min at 0<span class="elsevierStyleHsp" style=""></span>&#176;C and centrifuged for 10<span class="elsevierStyleHsp" style=""></span>min at 2000&#215;<span class="elsevierStyleItalic">g</span> at 25<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; The TBARS concentration was determined from reading the absorbance at 532<span class="elsevierStyleHsp" style=""></span>nm&#46; The population of 249 healthy individuals was used to determine the normal value&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical Analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">The results from both groups of individuals were compared using ANOVA&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#46; The association of <span class="elsevierStyleItalic">CAT</span> gene polymorphism -262 C&#47;T with bronchial asthma was determined using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test&#46; The genotype distribution was examined for deviation from the Hardy-Weinberg equilibrium&#46; To analyze the frequencies of the <span class="elsevierStyleItalic">CAT</span> genotypes in patients with bronchial asthma&#44; compared with healthy children&#44; the odds ratio &#40;OR&#41; and confidence intervals &#40;95&#37; CI&#41; were used&#46; Pearson&#39;s correlation was used to calculate the relationship between the oxidative stress markers and inflammatory markers in the expired air &#40;with Spearman&#39;s correlation when indicated&#41;&#46; All values are presented as mean&#177;SEM&#46; A <span class="elsevierStyleItalic">P</span> value &#60;&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Catalase Gene Polymorphism in Children With Bronchial Asthma and Healthy Individuals</span><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic and other characteristics of the study population&#46; A positive family history of asthma was detected in 92 asthmatic children &#40;37&#46;1&#37;&#41; and in 19 healthy children &#40;7&#46;6&#37;&#41;&#46; Based on a positive skin prick test with a standard panel of inhaled allergens&#44; 170 patients &#40;68&#46;5&#37;&#41; were atopic and 78 &#40;31&#46;5&#37;&#41; presented a non-atopic variant of asthma&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The genotype distribution and allele frequency in asthmatic and healthy children are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; A statistically significant difference was identified in the distribution of genotype polymorphisms of the <span class="elsevierStyleItalic">CAT</span> gene between asthmatic and healthy children&#46; In patients with bronchial asthma&#44; there was a higher prevalence of <span class="elsevierStyleItalic">CAT</span> genotype TT &#40;22&#46;6&#37;&#41; than in control individuals &#40;4&#46;8&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; There was a 5&#46;63-fold increase in the risk of asthma in the <span class="elsevierStyleItalic">CAT</span> TT genotype &#40;OR&#61;5&#46;63&#59; 95&#37; CI&#61;2&#46;93&#8211;10&#46;81&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; The coefficient of inbreeding &#40;consanguinity&#41; in control individuals was &#8722;0&#46;019 and 0&#46;610 in the cases&#46; The C allele was the most common in asthmatics &#40;72&#46;9&#37;&#41; and in healthy individuals &#40;69&#46;4&#37;&#41;&#46; The T allele represented a potential risk factor &#40;OR&#61;1&#46;49&#59; 95&#37; CI&#61;1&#46;12&#8211;1&#46;19&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;01&#41;&#46; The combination of the CC&#43;CT genotypes was shown to be a positive factor &#40;OR&#61;0&#46;178&#59; 95&#37; CI&#61;0&#46;65&#8211;1&#46;33&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#61;32&#46;10&#41;&#46; The combination of the heterozygous variant with the homozygous variant did not show any significant association&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">We separated the study population according to sex &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; No significant difference was found in the distribution of the <span class="elsevierStyleItalic">CAT</span> genotypes and alleles between asthmatic boys and girls&#46; A statistically significant difference was found in the distribution of the <span class="elsevierStyleItalic">CAT</span> genotypes and alleles when asthmatic boys or girls were compared with healthy boys or girls&#46; The homozygous variant was associated with bronchial asthma in both sexes &#40;OR&#61;7&#46;31&#59; 95&#37; CI&#61;2&#46;29&#8211;21&#46;49&#59; respectively&#44; OR&#61;4&#46;98&#59; 95&#37; CI&#61;2&#46;15&#8211;11&#46;53&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Effect of Catalase Gene Polymorphism on Protein Oxidative Damage and Lipid Peroxidation</span><p id="par0080" class="elsevierStylePara elsevierViewall">Greater oxidative damage of proteins and lipids was detected in children with bronchial asthma compared with healthy children &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The concentration of &#8211;SH groups decreased in the order of 18&#46;8&#37;&#177;0&#46;7&#37; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; in asthmatic children&#44; compared to control individuals&#46; There was no significant difference between the &#8211;SH group content between children with asthma exacerbations and controlled asthma&#46; No differences were observed in the control individuals in the concentration of &#8211;SH groups according to the <span class="elsevierStyleItalic">CAT</span> genotype &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A lower concentration of &#8211;SH groups was evident in patients with the <span class="elsevierStyleItalic">CAT</span> TT genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#44; compared to those with the CC and CT genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Oxidative stress caused an accumulation of TBARS in children with bronchial asthma&#46; The concentration of these substances increased by 29&#46;9&#37;&#177;3&#46;2&#37; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; in patients&#46; In patients with asthma exacerbation&#44; the lipid peroxidation markers increased significantly by 33&#46;0&#37;&#177;3&#46;0&#37;&#44; compared to patients whose asthma was stable &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#46; The TBARS values did not change according to the <span class="elsevierStyleItalic">CAT</span> genotype in healthy individuals &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In asthmatics with <span class="elsevierStyleItalic">CAT</span> genotype TT&#44; a higher concentration of TBARS was identified compared with the CC genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#44; and also with the CT genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">We found a significant correlation between markers of oxidative damage and inflammatory parameters in the expired air of asthmatic patients&#46; There was a slight significantly positive correlation between the TBARS concentration and the expired air markers &#40;FE<span class="elsevierStyleInf">NO</span> versus TBARS&#58; <span class="elsevierStyleItalic">r</span>&#61;0&#46;232 &#91;<span class="elsevierStyleItalic">P</span>&#61;&#46;002&#93;&#59; eCO versus TBARS&#58; <span class="elsevierStyleItalic">r</span>&#61;0&#46;147 &#91;<span class="elsevierStyleItalic">P</span>&#61;&#46;044&#93;&#41;&#46; A slight or moderately significant negative correlation was observed between the concentration of &#8211;SH groups and inflammatory markers &#40;FE<span class="elsevierStyleInf">NO</span> versus &#8211;SH&#58; <span class="elsevierStyleItalic">r</span>&#61;&#8722;0&#46;343 &#91;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#93;&#59; eCO versus &#8211;SH&#58; <span class="elsevierStyleItalic">r</span>&#61;&#8722;0&#46;232 &#91;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#93;&#41;&#46; These correlations were not observed in the control group&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Bronchial asthma is a complex immunological disease&#44; affected by environmental and genetic factors and their interactions&#44; which are probably key in its pathogenesis and prognosis&#46; Asthma belongs to a group of disorders in which oxidative damage and an imbalance between pro-oxidant and antioxidant substances play an important role&#46; We observed a higher prevalence of the TT genotype of the antioxidant enzyme CAT and an increase in the oxidative damage of proteins and lipids associated with bronchial asthma&#46; We also found that in asthmatic children with the <span class="elsevierStyleItalic">CAT</span> TT genotype&#44; there was greater oxidative damage compared with the other genetic variation of <span class="elsevierStyleItalic">CAT</span> -262 C&#47;T&#46; As far as the authors are aware&#44; this is the first study on the association of genetic polymorphism and oxidative damage in Slovakian children or adults with asthma&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Polymorphism of the genes involved in oxidative stress pathways&#44; NAD&#40;P&#41;H&#58;quinone oxidoreductase<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and glutathione transferases M1 and P1&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> have been associated with bronchial asthma&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> CAT is one of the essential antioxidant enzymes and&#44; therefore&#44; <span class="elsevierStyleItalic">CAT</span> is a candidate gene for many diseases that are potentially related with oxidative damage and exogenous&#47;endogenous oxidative stress&#46; In this study&#44; the frequency of the CAT TT genotype was 0&#46;226 in asthmatic children and 0&#46;048 in healthy children &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; The frequency of <span class="elsevierStyleItalic">CAT</span> genotype -262 C&#47;T was comparable to that described in other European Studies &#40;English&#44; German&#44; Polish and Turkish&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;21</span></a> Analysis according to sex showed similar results to the analysis of the total population&#44; and the homozygous variant was associated with bronchial asthma&#46; We have demonstrated that polymorphism in the <span class="elsevierStyleItalic">CAT</span> gene may be associated with a predisposition to bronchial asthma&#46; The homozygous variant <span class="elsevierStyleItalic">CAT</span> -262 C&#47;T was associated with asthma in white children of Hispanic origin but not in children of other origins&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Polonikov et al&#46; &#40;2009&#41; did not observe differences in the frequencies or genotype of CAT gene polymorphism -262 C&#47;T between asthmatic adults and healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> However&#44; an association was observed between <span class="elsevierStyleItalic">CAT</span> gene polymorphism -21A&#47;T and bronchial asthma&#44; and it was found that the risk of asthma in carriers of the -21AA genotype depends on exposure to both oxidants and antioxidants&#46; The contradictory results with respect to the relationship between the <span class="elsevierStyleItalic">CAT</span> gene polymorphism and bronchial asthma may be explained by the influence of the ethnicity&#46; In our selected population of Slovakian children&#44; the TT genotype was associated with bronchial asthma&#46; This genetic variation of the <span class="elsevierStyleItalic">CAT</span> gene could be responsible for oxidative damage&#44; as we observed an increase particularly in asthmatic children who were carriers of the TT genotype&#46; A decrease has been observed in CAT activity in the TT genotype in various studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;24&#44;25</span></a> However&#44; Forsberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> found a higher level of CAT in the <span class="elsevierStyleItalic">CAT</span> gene TT genotype&#46; The higher risk of asthma could be a result of the decreased CAT activity in the TT genotype&#44; and the subsequent increase in the oxidative damage of the biomolecules&#46; We observed an increase in protein and lipid oxidative damage in children with bronchial asthma&#46; Chronic inflammation is associated with higher production of ROS and an increase in oxidative stress in the lung&#46; Higher levels of hydrogen peroxide&#44; superoxide radical<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and lipid peroxidation<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a> have been found in children with bronchial asthma&#46; In the asthmatic population in the present study&#44; we observed an increase in nitric oxide<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and eCO&#46; These markers are characterized by a higher concentration in the TT genotype of asthmatic children compared with the CC and CT genotypes &#40;results not published&#41;&#46; It has been shown that the combination of the heterozygous variant with the homozygous variant is positive&#46; A C allele could be sufficient for CAT to function&#44; but further genetic studies are required to determine the activity and function of CAT in different genotypes&#44; not only for this polymorphism&#46; In healthy children with a variant of the <span class="elsevierStyleItalic">CAT</span> genotype&#44; other enzymatic antioxidants &#40;such as heme oxygenase&#44; superoxide dismutase&#44; glutathione peroxidase and glutathione transferase&#41; are detected in the normal homozygous form&#44; which protect them against oxidative damage&#46; Moreover&#44; healthy children do not show the increased ROS values detected in asthmatic children&#46; The relationship between oxidative damage and chronic inflammation in asthmatics is probably two-way&#46; Oxidative stress can exacerbate existing inflammation and can contribute to airway remodeling and conversely&#44; continuous chronic inflammation may result in increased production of ROS and greater oxidative damage&#46; In the control group&#44; comparison of the concentration of oxidative damage markers according to the CAT genotype did not reveal significant differences&#46; In this study&#44; the higher lipid peroxidation and protein modification detected could be a result of excessive ROS production or reduced capacity of the antioxidant defense system in asthmatics&#46; The antioxidants in food help endogenous antioxidants to prevent oxidative damage and represent a possible therapeutic option&#46; Antioxidant treatment could enhance reference asthma treatment and be an adjuvant&#44; especially in asthmatic patients with antioxidant enzyme risk genotypes&#46; Interactions between genes and environmental factors may influence CAT activity in the different genotypes&#46; We did not analyze these effects&#44; but it has been shown that exposure to smoke and the consumption of fruit and vegetables affect the activity of CAT in the CC&#44; CT and TT genotypes of the <span class="elsevierStyleItalic">CAT</span> gene&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#8211;26&#44;28</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Bronchial asthma is a complex&#44; multifactor disease in which genetic factors&#44; environmental factors and oxidative damage are responsible for its onset&#44; modulation and progression&#46; The results of this study show that polymorphisms of the <span class="elsevierStyleItalic">CAT</span> gene may be associated with bronchial asthma in children&#44; and could participate in greater oxidative damage&#46; The genetic variation in <span class="elsevierStyleItalic">CAT</span>&#44; which protects the cells against ROS&#44; may affect the asthmatic process&#46; In summary&#44; asthma is not an individual disease&#44; but a group of diseases associated with an increase in oxidative stress&#44; followed by the accumulation of oxidative damage&#46; This could be an important factor that contributes to the development and persistence of airway inflammation in asthmatic children&#46; Greater oxidative damage may be a consequence of cross reactions between polymorphism of the <span class="elsevierStyleItalic">CAT</span> gene and environmental factors&#44; as well as polymorphism of the CAT gene and other genetic factors that may modify the risk of disease&#46; However&#44; further studies on the interactions between polymorphism of the <span class="elsevierStyleItalic">CAT</span> gene and additional polymorphisms in genes related with asthma are required&#44; as they could help to improve our understanding of the complex disease that is bronchial asthma&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study was funded with a grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Ministry of Health</span> 2007&#47;47-UK-12&#44; and by the <span class="elsevierStyleGrantSponsor" id="gs0010">Ministry of Education&#44; Science&#44; Research and Sports of the Slovak Republic&#44; VEGA</span> 1&#47;0071&#47;11&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of Interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">None of the authors have declared any conflict of interests&#46;</p></span></span>"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Isolation of Deoxyribonucleic Acid"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Determination of Catalase Genotypes"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Plasma Protein Sulfhydryl Groups"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Lipid Peroxide Analysis"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Statistical Analysis"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Results"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Catalase Gene Polymorphism in Children With Bronchial Asthma and Healthy Individuals"
            ]
            1 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Effect of Catalase Gene Polymorphism on Protein Oxidative Damage and Lipid Peroxidation"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflict of Interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-01-30"
    "fechaAceptado" => "2013-04-04"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec279768"
          "palabras" => array:5 [
            0 => "Bronchial asthma"
            1 => "Catalase"
            2 => "Gene polymorphism"
            3 => "Oxidative damage"
            4 => "Children"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec279769"
          "palabras" => array:5 [
            0 => "Asma bronquial"
            1 => "Catalasa"
            2 => "Polimorfismo gen&#233;tico"
            3 => "Lesi&#243;n oxidativa"
            4 => "Ni&#241;os"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bronchial asthma is a complex disease in which genetic factors&#44; environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression&#46; If antioxidant mechanisms fail&#44; reactive oxygen species damage the biomolecules followed by progression of the disease&#46; Catalase is one of the most important endogenous enzymatic antioxidants&#46; In the present study&#44; we examined the hypothesis that increased oxidative damage and polymorphism in the <span class="elsevierStyleItalic">CAT</span> gene &#40;-262 promoter region&#44; C&#47;T&#41; are associated with childhood bronchial asthma&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Genotyping of the polymorphisms in the <span class="elsevierStyleItalic">CAT</span> gene in healthy &#40;249&#41; and asthmatic children &#40;248&#41; was performed using polymerase chain reaction &#8211; restriction fragment length polymorphism&#46; Markers of oxidative damage&#58; content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The TT genotype of catalase was more frequent among the asthmatic patients &#40;22&#46;6&#37;&#41; than in healthy children &#40;4&#46;8&#37;&#41; &#40;odds ratio&#61;5&#46;63&#59; 95&#37; confidence interval&#61;2&#46;93&#8211;10&#46;81&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; The amount of sulfhydryl groups decreased significantly and conversely&#44; the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children&#46; Genetic variation of enzymatic antioxidants may modulate disease risk&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El asma bronquial es una enfermedad compleja en la que los factores gen&#233;ticos&#44; los factores ambientales y la lesi&#243;n oxidativa son responsables del inicio y la modulaci&#243;n de su progresi&#243;n&#46; Si fracasan los mecanismos antioxidantes&#44; las especies reactivas del ox&#237;geno afectan a las biomol&#233;culas&#44; lo que se sigue de la progresi&#243;n de la enfermedad&#46; La catalasa es uno de los antioxidantes enzim&#225;ticos end&#243;genos m&#225;s importantes&#46; En el presente estudio examinamos la hip&#243;tesis de que un aumento de la lesi&#243;n oxidativa y el polimorfismo en el gen <span class="elsevierStyleItalic">CAT</span> &#40;regi&#243;n promotora -262 C&#47;T&#41; se asocian a asma bronquial infantil&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En ni&#241;os sanos &#40;249&#41; y ni&#241;os asm&#225;ticos &#40;248&#41; se efectu&#243; una genotipificaci&#243;n de los polimorfismos en el gen <span class="elsevierStyleItalic">CAT</span> usando la reacci&#243;n en cadena de la polimerasa-polimorfismo de longitud de fragmentos de restricci&#243;n&#46; Mediante espectrofotometr&#237;a&#44; en los ni&#241;os se analizaron los marcadores de lesi&#243;n oxidativa&#58; el contenido de grupos sulfhidrilo y de sustancias reactivas al &#225;cido tiobarbit&#250;rico&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El genotipo TT de la catalasa fue m&#225;s frecuente entre pacientes asm&#225;ticos &#40;22&#44;6&#37;&#41; que en ni&#241;os sanos &#40;4&#44;8&#37;&#41; &#40;<span class="elsevierStyleItalic">odds ratio</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#44;63&#59; intervalo de confianza del 95&#37;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;93&#8211;10&#44;81&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El contenido de grupos sulfhidrilo disminuy&#243; significativamente y&#44; al contrario&#44; el contenido de sustancias reactivas a &#225;cido tiobarbit&#250;rico aument&#243; significativamente en el asma bronquial y el genotipo TT de catalasa comparado con los otros genotipos catalasa de este gen&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los resultados del presente estudio sugieren que el polimorfismo del gen de la catalasa podr&#237;a participar en la aparici&#243;n de asma bronquial y en el aumento de la lesi&#243;n oxidativa en ni&#241;os asm&#225;ticos&#46; La variaci&#243;n gen&#233;tica de los antioxidantes enzim&#225;ticos podr&#237;a modular el riesgo de la enfermedad&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Babusikova E&#44; Jesenak M&#44; Evinova A&#44; Banovcin P&#44; Dobrota D&#46; Frecuencia del polimorfismo -262 <span class="elsevierStyleSmallCaps">C</span>&#47;T en el gen de la catalasa y lesi&#243;n oxidativa en ni&#241;os eslovacos con asma bronquial&#46; Arch Bronconeumol&#46; 2013&#59;49&#58;507&#8211;512&#46;</p>"
      ]
    ]
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Concentration of sulfhydryl groups &#40;&#8211;SH&#41;&#46; Comparison of the concentration of &#8211;SH in healthy individuals &#40;HI&#41; and children with bronchial asthma &#40;BA&#41; according to the catalase genotype&#46; &#42;&#42;&#42;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; comparison of the catalase genotypes&#44; <span class="elsevierStyleSup">&#8224;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CC genotype in patients&#44; <span class="elsevierStyleSup">&#167;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CT genotype in patients&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 918
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Concentration of thiobarbituric acid-reactive substances &#40;TBARS&#41;&#46; Comparison of the concentration of TBARS in healthy individuals &#40;HI&#41; and children with bronchial asthma &#40;BA&#41; according to the catalase genotype&#46; &#42;&#42;&#42;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; comparison of the catalase genotypes&#44; <span class="elsevierStyleSup">&#8224;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CC genotype in patients&#44; <span class="elsevierStyleSup">&#167;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CT genotype in patients&#46;</p>"
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        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">eCO&#44; expired carbon monoxide&#59; FE<span class="elsevierStyleInf">NO</span>&#44; fractional expired nitric oxide&#59; FEV<span class="elsevierStyleInf">1</span>&#44; forced expiratory volume in the first second&#59; ICS&#44; inhaled corticosteroids&#59; LABA&#44; long-acting beta<span class="elsevierStyleInf">2</span> agonists&#59; LTRA&#44; leukotriene receptor agonist&#59; n&#44; number of individuals&#59; ns&#44; not significant&#59; PEF&#44; peak expiratory flow&#59; ppb&#44; parts per billion&#59; ppm&#44; parts per million&#46;</p>"
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                  \t\t\t\t">248 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">249 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;28&#177;0&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age ranges &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#8211;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&#8211;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">170 &#40;68&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Family history of asthma&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">92 &#40;37&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Family history of atopy&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">133 &#40;53&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37 &#40;14&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t">84 &#40;33&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>LTRA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IC&#43;LABA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-histamines&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Treatment adherence&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FE<span class="elsevierStyleInf">NO</span> &#40;ppb&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>eCO &#40;ppm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;&#37; reference value&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">98&#46;04&#177;1&#46;54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> &#40;&#37; reference value&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">88&#46;95&#177;1&#46;98&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">97&#46;92&#177;3&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CI&#44; confidence interval&#59; n&#44; number of individuals&#59; OR&#44; <span class="elsevierStyleItalic">odds ratio</span>&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">The results of both groups of individuals were compared using ANOVA&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#46; The association of <span class="elsevierStyleItalic">CAT</span> gene polymorphism -262 C&#47;T with bronchial asthma was determined using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Healthy individuals &#40;n&#61;249&#41; &#37;&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Distribution of Genotypes and Alleles of the Catalase Gene &#40;<span class="elsevierStyleItalic">CAT</span>&#41; and Risk of Onset of Bronchial Asthma&#46;</p>"
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        "identificador" => "tbl0015"
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        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">CI&#44; confidence interval&#59; n&#44; number of individuals&#59; OR&#44; <span class="elsevierStyleItalic">odds ratio</span>&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">The results of both groups of individuals were compared using ANOVA&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#46; The association of <span class="elsevierStyleItalic">CAT</span> gene polymorphism -262 C&#47;T with bronchial asthma was determined using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Healthy individuals &#40;n&#61;249&#41; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>T allele&nbsp;\t\t\t\t\t\t\n
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Original Article
Frequency of Polymorphism -262 C/T in Catalase Gene and Oxidative Damage in Slovak Children With Bronchial Asthma
Frecuencia del polimorfismo -262 C/T en el gen de la catalasa y lesión oxidativa en niños eslovacos con asma bronquial
Eva Babusikovaa,
Corresponding author
babusikova@jfmed.uniba.sk

Corresponding author.
, Milos Jesenakb, Andrea Evinovaa, Peter Banovcina, Dusan Dobrotaa
a Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University de Bratislava, Martin, Slovak Republic
b Department of Pediatrics, Jessenius Faculty of Medicine, Comenius University de Bratislava, Martin, Slovak Republic
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    "titulo" => "Frequency of Polymorphism -262 C&#47;T in Catalase Gene and Oxidative Damage in Slovak Children With Bronchial Asthma"
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        "autoresLista" => "Eva Babusikova, Milos Jesenak, Andrea Evinova, Peter Banovcin, Dusan Dobrota"
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        "titulo" => "Frecuencia del polimorfismo -262 <span class="elsevierStyleSmallCaps">C</span>&#47;T en el gen de la catalasa y lesi&#243;n oxidativa en ni&#241;os eslovacos con asma bronquial"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Concentration of thiobarbituric acid-reactive substances &#40;TBARS&#41;&#46; Comparison of the concentration of TBARS in healthy individuals &#40;HI&#41; and children with bronchial asthma &#40;BA&#41; according to the catalase genotype&#46; &#42;&#42;&#42;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; comparison of the catalase genotypes&#44; <span class="elsevierStyleSup">&#8224;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CC genotype in patients&#44; <span class="elsevierStyleSup">&#167;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CT genotype in patients&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bronchial asthma is a chronic&#44; complex&#44; heterogeneous disease of the airways&#44; which includes the activation of many inflammatory and structural cell populations that release numerous inflammatory mediators&#44; giving rise to the physiopathological changes that are characteristic of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Environmental and genetic factors play a role in its onset&#44; although the exact mechanisms of their actions have not been fully determined&#46; The lungs are continually exposed to oxidants generated endogenously from the mitochondria&#44; phagocytes and other cells&#44; or exogenously from air pollutants and cigarette smoke&#46; They have the largest endothelial surface area of any organ&#44; which makes the lung tissue the principal target for circulating oxidants and xenobiotics&#46; Asthmatic patients produce a variety of mediators&#44; including reactive oxygen species &#40;ROS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> An increase in oxidative damage can contribute to both the origin and development of respiratory diseases&#44; including bronchial asthma&#46; Lung lesions due to ROS are related with the oxidation of deoxyribonucleic acid &#40;DNA&#41;&#44; proteins and lipids&#46; These oxidized biomolecules can induce various responses and a cascade of events&#44; such as airway hyperreactivity&#44; increase in the generation of chemoattractants&#44; release of tachykinins and neurokinins&#44; and an increase in the release of mediators which ultimately aggravate the oxidative damage&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The lungs can use non-enzymatic antioxidants&#44; such as vitamins&#44; uric acid&#44; glutathione&#44; sulfhydryl groups &#40;proteins&#44; peptides and amino acids&#41; and various enzymatic antioxidants&#44; such as superoxide dismutase&#44; catalase &#40;CAT&#41; and glutathione peroxidase as a defense against oxidative damage and ROS&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">CAT &#40;EC 1&#46;11&#46;1&#46;6&#41; is a common antioxidant enzyme responsible for controlling the hydrogen peroxide concentrations in cells&#46; It is ubiquitous in most aerobic cells also detected in the lungs &#40;macrophages&#44; fibroblasts and pneumocytes&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> As an intracellular antioxidant enzyme&#44; CAT catalyses the breakdown of two hydrogen peroxide molecules into one oxygen molecule and two water molecules&#59; its activity is determined genetically&#46; The <span class="elsevierStyleItalic">CAT</span> gene is located on chromosome 11p13&#59; it is 34<span class="elsevierStyleHsp" style=""></span>kb long&#44; contains 13 exons and 12 introns and codes a 256-amino acid protein&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> Various polymorphisms of this enzyme have been described and characterized&#44; both in the coding<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> and non-coding region&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#8211;11</span></a> A common polymorphism in the <span class="elsevierStyleItalic">CAT</span> gene promoter region is the substitution of T for C in position T -262 in the 5&#8242; region&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> which is considered to lead to a decrease in enzyme activity&#46; The <span class="elsevierStyleItalic">CAT</span> TT genotype could be responsible for a reduction in the antioxidant defense and a subsequent increase in oxidative damage&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Since oxidative damage plays a role in the pathogenesis of asthma&#44; and CAT is critical for protecting cells against ROS&#44; we hypothesized that the polymorphisms in the CAT gene that influence its enzyme activity contribute substantially to the onset of the disease&#46; This study aimed to evaluate <span class="elsevierStyleItalic">CAT</span> polymorphism -262 C&#47;T in asthmatic children&#46; We sought to determine markers of oxidative damage&#44; and to analyze a possible association between the <span class="elsevierStyleItalic">CAT</span> genotype and oxidative damage of proteins and lipids in asthmatic and healthy children&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study Individuals</span><p id="par0020" class="elsevierStylePara elsevierViewall">The study population consisted of 457 children&#46; Using the categories from reference questionnaires&#44; the asthma history of the children was recorded&#58; age&#44; sex&#44; exposure to cigarette smoke and family history of asthma&#44; wheezing and allergy&#46; The children or their parents completed the Asthma control test<span class="elsevierStyleSup">&#174;</span>&#46; Active smokers and children exposed to passive smoking were then excluded from the study&#46; The 248 asthma patients &#40;58&#37; boys and 42&#37; girls&#41; were enrolled from the Pediatrics Department of Martin University Hospital &#40;Slovakia&#41;&#46; During routine health checks&#44; general practitioners recruited a further 249 healthy children of comparable age and sex &#40;54&#37; boys and 46&#37; girls&#41;&#46; The children did not present any clinical symptoms of allergic diseases and had no history of serious illness&#46; Asthmatic children who participated in the study were characterized by recurrent airway obstruction&#44; manifested by wheezing and dyspnea&#44; with spontaneous relief with bronchodilator treatment &#40;as defined in the Global Asthma Initiative&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">All children underwent fractional expired nitric oxide &#40;FE<span class="elsevierStyleInf">NO</span>&#41; and expired carbon monoxide &#40;eCO&#41; analyses&#46; The FE<span class="elsevierStyleInf">NO</span> was determined according to American Thoracic Society&#47;European Respiratory Society &#40;ATS&#47;ERS&#41; standards<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> using a portable nitric oxide analyzer &#40;NIOX-MINO<span class="elsevierStyleSup">&#174;</span>&#44; Aerocrine&#44; Sweden&#41;&#46; The eCO was analyzed using a Micro 4 Smokerlyzer<span class="elsevierStyleSup">&#174;</span> &#40;Bedfont&#44; England&#41;&#46; We also carried out basic spirometry &#40;KoKo DigiDoser-Spirometer&#44; nSpire Health&#44; Louisville&#44; United States&#41;&#44; in accordance with ATS&#47;ERS recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The FE<span class="elsevierStyleInf">NO</span> and eCO values were estimated before the spirometer test&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The study was approved by the Jessenius Faculty of Medicine&#44; Martin&#44; and written informed consent was obtained from the parents of all the children examined&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Isolation of Deoxyribonucleic Acid</span><p id="par0035" class="elsevierStylePara elsevierViewall">Blood samples were extracted into ethylene-diamine-tetraacetic acid &#40;EDTA&#41; tubes&#46; The genomic DNA was prepared using blood according to a commercial procedure &#40;Wizard<span class="elsevierStyleSup">&#174;</span> Genomic DNA purification kit&#44; Promega&#44; Madison&#44; USA&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Determination of Catalase Genotypes</span><p id="par0040" class="elsevierStylePara elsevierViewall">All DNA samples from asthmatic and healthy children were genotyped by polymerase chain reaction &#40;PCR&#41;&#44; followed by restriction fragment length polymorphism &#40;RFLP&#41; analysis&#46; CAT polymorphism -262 C&#47;T &#40;rs 1001179&#41; was determined using direct primer 5&#8242;-AGAGCCTCGCCCCGCCGGACCG-3&#8242; and CAT reverse primer 5&#8242;-TAAGAGCAGAGAAAGCATAGCT-3&#8242;&#46; PCR products of 185<span class="elsevierStyleHsp" style=""></span>bp were digested using the restriction enzyme Smal&#46; The products were visualized by 2&#37; agarose gel electrophoresis&#46; The wild-type CC genotype appeared as 155 and 30<span class="elsevierStyleHsp" style=""></span>bp fragments&#44; and the CT genotype as 185&#44; 155 and 30<span class="elsevierStyleHsp" style=""></span>bp fragments&#46; TT genotypes were not digested by Smal &#40;185<span class="elsevierStyleHsp" style=""></span>bp&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Plasma Protein Sulfhydryl Groups</span><p id="par0045" class="elsevierStylePara elsevierViewall">Plasma for determination of protein and lipid markers of oxidative damage was obtained from blood prepared by centrifugation for 20<span class="elsevierStyleHsp" style=""></span>min&#44; at 2000&#215;<span class="elsevierStyleItalic">g</span> at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The total concentration of reduced sulfhydryl groups &#40;&#8722;SH&#44; proteins&#44; oligopeptides&#44; glutathione and amino acids&#41; was determined by spectrophotometry&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Two ml of Ellman&#39;s reagent &#40;0&#46;250<span class="elsevierStyleHsp" style=""></span>mol&#47;l of Tris&#8211;HCl&#59; pH 8&#46;2&#44; 10<span class="elsevierStyleHsp" style=""></span>mmol&#47;l of 5&#46;5&#8242;-dithiobis-2-nitrobenzoic acid&#41; were added to 100<span class="elsevierStyleHsp" style=""></span>&#956;l of sample and incubated for 15<span class="elsevierStyleHsp" style=""></span>min at room temperature&#46; The absorbance was read at 412<span class="elsevierStyleHsp" style=""></span>nm and &#8211;SH group content was calculated using the molar absorption coefficient of 13<span class="elsevierStyleHsp" style=""></span>600<span class="elsevierStyleHsp" style=""></span>M<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">&#8722;1</span> after subtracting the absorbance of the blank from the sample absorbance&#46; A population of 249 healthy individuals was used to determine the normal value&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Lipid Peroxide Analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Modifications in the structure of the plasma lipids were analyzed by determining the thiobarbituric acid-reactive substances &#40;TBARS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> A sample was incubated with ethanol&#44; 14&#37; trichloroacetic acid and 0&#46;6&#37; thiobarbituric acid at 80<span class="elsevierStyleHsp" style=""></span>&#176;C for 30<span class="elsevierStyleHsp" style=""></span>min&#46; It was then incubated for 5<span class="elsevierStyleHsp" style=""></span>min at 0<span class="elsevierStyleHsp" style=""></span>&#176;C and centrifuged for 10<span class="elsevierStyleHsp" style=""></span>min at 2000&#215;<span class="elsevierStyleItalic">g</span> at 25<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; The TBARS concentration was determined from reading the absorbance at 532<span class="elsevierStyleHsp" style=""></span>nm&#46; The population of 249 healthy individuals was used to determine the normal value&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical Analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">The results from both groups of individuals were compared using ANOVA&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#46; The association of <span class="elsevierStyleItalic">CAT</span> gene polymorphism -262 C&#47;T with bronchial asthma was determined using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test&#46; The genotype distribution was examined for deviation from the Hardy-Weinberg equilibrium&#46; To analyze the frequencies of the <span class="elsevierStyleItalic">CAT</span> genotypes in patients with bronchial asthma&#44; compared with healthy children&#44; the odds ratio &#40;OR&#41; and confidence intervals &#40;95&#37; CI&#41; were used&#46; Pearson&#39;s correlation was used to calculate the relationship between the oxidative stress markers and inflammatory markers in the expired air &#40;with Spearman&#39;s correlation when indicated&#41;&#46; All values are presented as mean&#177;SEM&#46; A <span class="elsevierStyleItalic">P</span> value &#60;&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Catalase Gene Polymorphism in Children With Bronchial Asthma and Healthy Individuals</span><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the demographic and other characteristics of the study population&#46; A positive family history of asthma was detected in 92 asthmatic children &#40;37&#46;1&#37;&#41; and in 19 healthy children &#40;7&#46;6&#37;&#41;&#46; Based on a positive skin prick test with a standard panel of inhaled allergens&#44; 170 patients &#40;68&#46;5&#37;&#41; were atopic and 78 &#40;31&#46;5&#37;&#41; presented a non-atopic variant of asthma&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The genotype distribution and allele frequency in asthmatic and healthy children are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; A statistically significant difference was identified in the distribution of genotype polymorphisms of the <span class="elsevierStyleItalic">CAT</span> gene between asthmatic and healthy children&#46; In patients with bronchial asthma&#44; there was a higher prevalence of <span class="elsevierStyleItalic">CAT</span> genotype TT &#40;22&#46;6&#37;&#41; than in control individuals &#40;4&#46;8&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; There was a 5&#46;63-fold increase in the risk of asthma in the <span class="elsevierStyleItalic">CAT</span> TT genotype &#40;OR&#61;5&#46;63&#59; 95&#37; CI&#61;2&#46;93&#8211;10&#46;81&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; The coefficient of inbreeding &#40;consanguinity&#41; in control individuals was &#8722;0&#46;019 and 0&#46;610 in the cases&#46; The C allele was the most common in asthmatics &#40;72&#46;9&#37;&#41; and in healthy individuals &#40;69&#46;4&#37;&#41;&#46; The T allele represented a potential risk factor &#40;OR&#61;1&#46;49&#59; 95&#37; CI&#61;1&#46;12&#8211;1&#46;19&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;01&#41;&#46; The combination of the CC&#43;CT genotypes was shown to be a positive factor &#40;OR&#61;0&#46;178&#59; 95&#37; CI&#61;0&#46;65&#8211;1&#46;33&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#61;32&#46;10&#41;&#46; The combination of the heterozygous variant with the homozygous variant did not show any significant association&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">We separated the study population according to sex &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; No significant difference was found in the distribution of the <span class="elsevierStyleItalic">CAT</span> genotypes and alleles between asthmatic boys and girls&#46; A statistically significant difference was found in the distribution of the <span class="elsevierStyleItalic">CAT</span> genotypes and alleles when asthmatic boys or girls were compared with healthy boys or girls&#46; The homozygous variant was associated with bronchial asthma in both sexes &#40;OR&#61;7&#46;31&#59; 95&#37; CI&#61;2&#46;29&#8211;21&#46;49&#59; respectively&#44; OR&#61;4&#46;98&#59; 95&#37; CI&#61;2&#46;15&#8211;11&#46;53&#59; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Effect of Catalase Gene Polymorphism on Protein Oxidative Damage and Lipid Peroxidation</span><p id="par0080" class="elsevierStylePara elsevierViewall">Greater oxidative damage of proteins and lipids was detected in children with bronchial asthma compared with healthy children &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; The concentration of &#8211;SH groups decreased in the order of 18&#46;8&#37;&#177;0&#46;7&#37; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; in asthmatic children&#44; compared to control individuals&#46; There was no significant difference between the &#8211;SH group content between children with asthma exacerbations and controlled asthma&#46; No differences were observed in the control individuals in the concentration of &#8211;SH groups according to the <span class="elsevierStyleItalic">CAT</span> genotype &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A lower concentration of &#8211;SH groups was evident in patients with the <span class="elsevierStyleItalic">CAT</span> TT genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#44; compared to those with the CC and CT genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Oxidative stress caused an accumulation of TBARS in children with bronchial asthma&#46; The concentration of these substances increased by 29&#46;9&#37;&#177;3&#46;2&#37; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; in patients&#46; In patients with asthma exacerbation&#44; the lipid peroxidation markers increased significantly by 33&#46;0&#37;&#177;3&#46;0&#37;&#44; compared to patients whose asthma was stable &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#46; The TBARS values did not change according to the <span class="elsevierStyleItalic">CAT</span> genotype in healthy individuals &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In asthmatics with <span class="elsevierStyleItalic">CAT</span> genotype TT&#44; a higher concentration of TBARS was identified compared with the CC genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#44; and also with the CT genotype &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">We found a significant correlation between markers of oxidative damage and inflammatory parameters in the expired air of asthmatic patients&#46; There was a slight significantly positive correlation between the TBARS concentration and the expired air markers &#40;FE<span class="elsevierStyleInf">NO</span> versus TBARS&#58; <span class="elsevierStyleItalic">r</span>&#61;0&#46;232 &#91;<span class="elsevierStyleItalic">P</span>&#61;&#46;002&#93;&#59; eCO versus TBARS&#58; <span class="elsevierStyleItalic">r</span>&#61;0&#46;147 &#91;<span class="elsevierStyleItalic">P</span>&#61;&#46;044&#93;&#41;&#46; A slight or moderately significant negative correlation was observed between the concentration of &#8211;SH groups and inflammatory markers &#40;FE<span class="elsevierStyleInf">NO</span> versus &#8211;SH&#58; <span class="elsevierStyleItalic">r</span>&#61;&#8722;0&#46;343 &#91;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#93;&#59; eCO versus &#8211;SH&#58; <span class="elsevierStyleItalic">r</span>&#61;&#8722;0&#46;232 &#91;<span class="elsevierStyleItalic">P</span>&#61;&#46;001&#93;&#41;&#46; These correlations were not observed in the control group&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">Bronchial asthma is a complex immunological disease&#44; affected by environmental and genetic factors and their interactions&#44; which are probably key in its pathogenesis and prognosis&#46; Asthma belongs to a group of disorders in which oxidative damage and an imbalance between pro-oxidant and antioxidant substances play an important role&#46; We observed a higher prevalence of the TT genotype of the antioxidant enzyme CAT and an increase in the oxidative damage of proteins and lipids associated with bronchial asthma&#46; We also found that in asthmatic children with the <span class="elsevierStyleItalic">CAT</span> TT genotype&#44; there was greater oxidative damage compared with the other genetic variation of <span class="elsevierStyleItalic">CAT</span> -262 C&#47;T&#46; As far as the authors are aware&#44; this is the first study on the association of genetic polymorphism and oxidative damage in Slovakian children or adults with asthma&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Polymorphism of the genes involved in oxidative stress pathways&#44; NAD&#40;P&#41;H&#58;quinone oxidoreductase<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and glutathione transferases M1 and P1&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> have been associated with bronchial asthma&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a> CAT is one of the essential antioxidant enzymes and&#44; therefore&#44; <span class="elsevierStyleItalic">CAT</span> is a candidate gene for many diseases that are potentially related with oxidative damage and exogenous&#47;endogenous oxidative stress&#46; In this study&#44; the frequency of the CAT TT genotype was 0&#46;226 in asthmatic children and 0&#46;048 in healthy children &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; The frequency of <span class="elsevierStyleItalic">CAT</span> genotype -262 C&#47;T was comparable to that described in other European Studies &#40;English&#44; German&#44; Polish and Turkish&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;21</span></a> Analysis according to sex showed similar results to the analysis of the total population&#44; and the homozygous variant was associated with bronchial asthma&#46; We have demonstrated that polymorphism in the <span class="elsevierStyleItalic">CAT</span> gene may be associated with a predisposition to bronchial asthma&#46; The homozygous variant <span class="elsevierStyleItalic">CAT</span> -262 C&#47;T was associated with asthma in white children of Hispanic origin but not in children of other origins&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Polonikov et al&#46; &#40;2009&#41; did not observe differences in the frequencies or genotype of CAT gene polymorphism -262 C&#47;T between asthmatic adults and healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> However&#44; an association was observed between <span class="elsevierStyleItalic">CAT</span> gene polymorphism -21A&#47;T and bronchial asthma&#44; and it was found that the risk of asthma in carriers of the -21AA genotype depends on exposure to both oxidants and antioxidants&#46; The contradictory results with respect to the relationship between the <span class="elsevierStyleItalic">CAT</span> gene polymorphism and bronchial asthma may be explained by the influence of the ethnicity&#46; In our selected population of Slovakian children&#44; the TT genotype was associated with bronchial asthma&#46; This genetic variation of the <span class="elsevierStyleItalic">CAT</span> gene could be responsible for oxidative damage&#44; as we observed an increase particularly in asthmatic children who were carriers of the TT genotype&#46; A decrease has been observed in CAT activity in the TT genotype in various studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;24&#44;25</span></a> However&#44; Forsberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> found a higher level of CAT in the <span class="elsevierStyleItalic">CAT</span> gene TT genotype&#46; The higher risk of asthma could be a result of the decreased CAT activity in the TT genotype&#44; and the subsequent increase in the oxidative damage of the biomolecules&#46; We observed an increase in protein and lipid oxidative damage in children with bronchial asthma&#46; Chronic inflammation is associated with higher production of ROS and an increase in oxidative stress in the lung&#46; Higher levels of hydrogen peroxide&#44; superoxide radical<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and lipid peroxidation<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a> have been found in children with bronchial asthma&#46; In the asthmatic population in the present study&#44; we observed an increase in nitric oxide<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and eCO&#46; These markers are characterized by a higher concentration in the TT genotype of asthmatic children compared with the CC and CT genotypes &#40;results not published&#41;&#46; It has been shown that the combination of the heterozygous variant with the homozygous variant is positive&#46; A C allele could be sufficient for CAT to function&#44; but further genetic studies are required to determine the activity and function of CAT in different genotypes&#44; not only for this polymorphism&#46; In healthy children with a variant of the <span class="elsevierStyleItalic">CAT</span> genotype&#44; other enzymatic antioxidants &#40;such as heme oxygenase&#44; superoxide dismutase&#44; glutathione peroxidase and glutathione transferase&#41; are detected in the normal homozygous form&#44; which protect them against oxidative damage&#46; Moreover&#44; healthy children do not show the increased ROS values detected in asthmatic children&#46; The relationship between oxidative damage and chronic inflammation in asthmatics is probably two-way&#46; Oxidative stress can exacerbate existing inflammation and can contribute to airway remodeling and conversely&#44; continuous chronic inflammation may result in increased production of ROS and greater oxidative damage&#46; In the control group&#44; comparison of the concentration of oxidative damage markers according to the CAT genotype did not reveal significant differences&#46; In this study&#44; the higher lipid peroxidation and protein modification detected could be a result of excessive ROS production or reduced capacity of the antioxidant defense system in asthmatics&#46; The antioxidants in food help endogenous antioxidants to prevent oxidative damage and represent a possible therapeutic option&#46; Antioxidant treatment could enhance reference asthma treatment and be an adjuvant&#44; especially in asthmatic patients with antioxidant enzyme risk genotypes&#46; Interactions between genes and environmental factors may influence CAT activity in the different genotypes&#46; We did not analyze these effects&#44; but it has been shown that exposure to smoke and the consumption of fruit and vegetables affect the activity of CAT in the CC&#44; CT and TT genotypes of the <span class="elsevierStyleItalic">CAT</span> gene&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#8211;26&#44;28</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Bronchial asthma is a complex&#44; multifactor disease in which genetic factors&#44; environmental factors and oxidative damage are responsible for its onset&#44; modulation and progression&#46; The results of this study show that polymorphisms of the <span class="elsevierStyleItalic">CAT</span> gene may be associated with bronchial asthma in children&#44; and could participate in greater oxidative damage&#46; The genetic variation in <span class="elsevierStyleItalic">CAT</span>&#44; which protects the cells against ROS&#44; may affect the asthmatic process&#46; In summary&#44; asthma is not an individual disease&#44; but a group of diseases associated with an increase in oxidative stress&#44; followed by the accumulation of oxidative damage&#46; This could be an important factor that contributes to the development and persistence of airway inflammation in asthmatic children&#46; Greater oxidative damage may be a consequence of cross reactions between polymorphism of the <span class="elsevierStyleItalic">CAT</span> gene and environmental factors&#44; as well as polymorphism of the CAT gene and other genetic factors that may modify the risk of disease&#46; However&#44; further studies on the interactions between polymorphism of the <span class="elsevierStyleItalic">CAT</span> gene and additional polymorphisms in genes related with asthma are required&#44; as they could help to improve our understanding of the complex disease that is bronchial asthma&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study was funded with a grant from the <span class="elsevierStyleGrantSponsor" id="gs0005">Ministry of Health</span> 2007&#47;47-UK-12&#44; and by the <span class="elsevierStyleGrantSponsor" id="gs0010">Ministry of Education&#44; Science&#44; Research and Sports of the Slovak Republic&#44; VEGA</span> 1&#47;0071&#47;11&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of Interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">None of the authors have declared any conflict of interests&#46;</p></span></span>"
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        0 => array:2 [
          "identificador" => "xres296095"
          "titulo" => array:5 [
            0 => "Abstract"
            1 => "Introduction"
            2 => "Patients and methods"
            3 => "Results"
            4 => "Conclusions"
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        ]
        1 => array:2 [
          "identificador" => "xpalclavsec279768"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
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          "titulo" => array:5 [
            0 => "Resumen"
            1 => "Introducci&#243;n"
            2 => "Pacientes y m&#233;todos"
            3 => "Resultados"
            4 => "Conclusiones"
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        ]
        3 => array:2 [
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          "titulo" => "Palabras clave"
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          "titulo" => "Introduction"
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        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Patients and Methods"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Study Individuals"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Isolation of Deoxyribonucleic Acid"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Determination of Catalase Genotypes"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Plasma Protein Sulfhydryl Groups"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Lipid Peroxide Analysis"
            ]
            5 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Statistical Analysis"
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        6 => array:3 [
          "identificador" => "sec0045"
          "titulo" => "Results"
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            0 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Catalase Gene Polymorphism in Children With Bronchial Asthma and Healthy Individuals"
            ]
            1 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Effect of Catalase Gene Polymorphism on Protein Oxidative Damage and Lipid Peroxidation"
            ]
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          "titulo" => "Discussion"
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          "titulo" => "Funding"
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          "identificador" => "sec0070"
          "titulo" => "Conflict of Interest"
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        10 => array:1 [
          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2013-01-30"
    "fechaAceptado" => "2013-04-04"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec279768"
          "palabras" => array:5 [
            0 => "Bronchial asthma"
            1 => "Catalase"
            2 => "Gene polymorphism"
            3 => "Oxidative damage"
            4 => "Children"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec279769"
          "palabras" => array:5 [
            0 => "Asma bronquial"
            1 => "Catalasa"
            2 => "Polimorfismo gen&#233;tico"
            3 => "Lesi&#243;n oxidativa"
            4 => "Ni&#241;os"
          ]
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bronchial asthma is a complex disease in which genetic factors&#44; environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression&#46; If antioxidant mechanisms fail&#44; reactive oxygen species damage the biomolecules followed by progression of the disease&#46; Catalase is one of the most important endogenous enzymatic antioxidants&#46; In the present study&#44; we examined the hypothesis that increased oxidative damage and polymorphism in the <span class="elsevierStyleItalic">CAT</span> gene &#40;-262 promoter region&#44; C&#47;T&#41; are associated with childhood bronchial asthma&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Genotyping of the polymorphisms in the <span class="elsevierStyleItalic">CAT</span> gene in healthy &#40;249&#41; and asthmatic children &#40;248&#41; was performed using polymerase chain reaction &#8211; restriction fragment length polymorphism&#46; Markers of oxidative damage&#58; content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The TT genotype of catalase was more frequent among the asthmatic patients &#40;22&#46;6&#37;&#41; than in healthy children &#40;4&#46;8&#37;&#41; &#40;odds ratio&#61;5&#46;63&#59; 95&#37; confidence interval&#61;2&#46;93&#8211;10&#46;81&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; The amount of sulfhydryl groups decreased significantly and conversely&#44; the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children&#46; Genetic variation of enzymatic antioxidants may modulate disease risk&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El asma bronquial es una enfermedad compleja en la que los factores gen&#233;ticos&#44; los factores ambientales y la lesi&#243;n oxidativa son responsables del inicio y la modulaci&#243;n de su progresi&#243;n&#46; Si fracasan los mecanismos antioxidantes&#44; las especies reactivas del ox&#237;geno afectan a las biomol&#233;culas&#44; lo que se sigue de la progresi&#243;n de la enfermedad&#46; La catalasa es uno de los antioxidantes enzim&#225;ticos end&#243;genos m&#225;s importantes&#46; En el presente estudio examinamos la hip&#243;tesis de que un aumento de la lesi&#243;n oxidativa y el polimorfismo en el gen <span class="elsevierStyleItalic">CAT</span> &#40;regi&#243;n promotora -262 C&#47;T&#41; se asocian a asma bronquial infantil&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">En ni&#241;os sanos &#40;249&#41; y ni&#241;os asm&#225;ticos &#40;248&#41; se efectu&#243; una genotipificaci&#243;n de los polimorfismos en el gen <span class="elsevierStyleItalic">CAT</span> usando la reacci&#243;n en cadena de la polimerasa-polimorfismo de longitud de fragmentos de restricci&#243;n&#46; Mediante espectrofotometr&#237;a&#44; en los ni&#241;os se analizaron los marcadores de lesi&#243;n oxidativa&#58; el contenido de grupos sulfhidrilo y de sustancias reactivas al &#225;cido tiobarbit&#250;rico&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El genotipo TT de la catalasa fue m&#225;s frecuente entre pacientes asm&#225;ticos &#40;22&#44;6&#37;&#41; que en ni&#241;os sanos &#40;4&#44;8&#37;&#41; &#40;<span class="elsevierStyleItalic">odds ratio</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#44;63&#59; intervalo de confianza del 95&#37;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;93&#8211;10&#44;81&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El contenido de grupos sulfhidrilo disminuy&#243; significativamente y&#44; al contrario&#44; el contenido de sustancias reactivas a &#225;cido tiobarbit&#250;rico aument&#243; significativamente en el asma bronquial y el genotipo TT de catalasa comparado con los otros genotipos catalasa de este gen&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los resultados del presente estudio sugieren que el polimorfismo del gen de la catalasa podr&#237;a participar en la aparici&#243;n de asma bronquial y en el aumento de la lesi&#243;n oxidativa en ni&#241;os asm&#225;ticos&#46; La variaci&#243;n gen&#233;tica de los antioxidantes enzim&#225;ticos podr&#237;a modular el riesgo de la enfermedad&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Babusikova E&#44; Jesenak M&#44; Evinova A&#44; Banovcin P&#44; Dobrota D&#46; Frecuencia del polimorfismo -262 <span class="elsevierStyleSmallCaps">C</span>&#47;T en el gen de la catalasa y lesi&#243;n oxidativa en ni&#241;os eslovacos con asma bronquial&#46; Arch Bronconeumol&#46; 2013&#59;49&#58;507&#8211;512&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Concentration of sulfhydryl groups &#40;&#8211;SH&#41;&#46; Comparison of the concentration of &#8211;SH in healthy individuals &#40;HI&#41; and children with bronchial asthma &#40;BA&#41; according to the catalase genotype&#46; &#42;&#42;&#42;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; comparison of the catalase genotypes&#44; <span class="elsevierStyleSup">&#8224;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CC genotype in patients&#44; <span class="elsevierStyleSup">&#167;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CT genotype in patients&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Concentration of thiobarbituric acid-reactive substances &#40;TBARS&#41;&#46; Comparison of the concentration of TBARS in healthy individuals &#40;HI&#41; and children with bronchial asthma &#40;BA&#41; according to the catalase genotype&#46; &#42;&#42;&#42;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#44; comparison of the catalase genotypes&#44; <span class="elsevierStyleSup">&#8224;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CC genotype in patients&#44; <span class="elsevierStyleSup">&#167;</span><span class="elsevierStyleItalic">P</span>&#60;&#46;05&#44; comparison of the catalase TT genotype versus the CT genotype in patients&#46;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">eCO&#44; expired carbon monoxide&#59; FE<span class="elsevierStyleInf">NO</span>&#44; fractional expired nitric oxide&#59; FEV<span class="elsevierStyleInf">1</span>&#44; forced expiratory volume in the first second&#59; ICS&#44; inhaled corticosteroids&#59; LABA&#44; long-acting beta<span class="elsevierStyleInf">2</span> agonists&#59; LTRA&#44; leukotriene receptor agonist&#59; n&#44; number of individuals&#59; ns&#44; not significant&#59; PEF&#44; peak expiratory flow&#59; ppb&#44; parts per billion&#59; ppm&#44; parts per million&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">117 &#40;47&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Females&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">107 &#40;43&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">132 &#40;53&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12&#46;28&#177;0&#46;24&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13&#46;14&#177;0&#46;48&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age ranges &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">5&#8211;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#8211;19&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ns&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Atopy&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">170 &#40;68&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Family history of asthma&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">92 &#40;37&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">19 &#40;7&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Family history of atopy&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">133 &#40;53&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">37 &#40;14&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age at the time of bronchial asthma diagnosis&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">7&#46;14&#177;2&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Controlled asthma&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">216 &#40;87&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Uncontrolled asthma&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">32 &#40;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Treatment</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ICS&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">84 &#40;33&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>LTRA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93 &#40;37&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IC&#43;LABA&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">113 &#40;45&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anti-histamines&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">226 &#40;91&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Treatment adherence&#44; n &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">228 &#40;91&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Inflammatory markers</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FE<span class="elsevierStyleInf">NO</span> &#40;ppb&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">25&#46;98&#177;1&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12&#46;57&#177;0&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>eCO &#40;ppm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#46;44&#177;0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;91&#177;0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Lung function tests</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span> &#40;&#37; reference value&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&#46;04&#177;1&#46;54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> &#40;&#37; reference value&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">88&#46;95&#177;1&#46;98&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#46;92&#177;3&#46;12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">P</span>&#60;&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">General Characteristics of the Study Population&#46;</p>"
        ]
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CI&#44; confidence interval&#59; n&#44; number of individuals&#59; OR&#44; <span class="elsevierStyleItalic">odds ratio</span>&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">The results of both groups of individuals were compared using ANOVA&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#46; The association of <span class="elsevierStyleItalic">CAT</span> gene polymorphism -262 C&#47;T with bronchial asthma was determined using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">CAT</span> -262 C&#47;T&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Healthy individuals &#40;n&#61;249&#41; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Asthmatic individuals &#40;n&#61;248&#41; &#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">95&#37; CI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;23&#8211;0&#46;54&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">TT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">22&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">5&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;93&#8211;10&#46;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C allele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">72&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">69&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;50&#8211;0&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T allele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;12&#8211;1&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Distribution of Genotypes and Alleles of the Catalase Gene &#40;<span class="elsevierStyleItalic">CAT</span>&#41; and Risk of Onset of Bronchial Asthma&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">CI&#44; confidence interval&#59; n&#44; number of individuals&#59; OR&#44; <span class="elsevierStyleItalic">odds ratio</span>&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">The results of both groups of individuals were compared using ANOVA&#44; the Student&#39;s <span class="elsevierStyleItalic">t</span>-test and Chi-squared test &#40;<span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#41;&#46; The association of <span class="elsevierStyleItalic">CAT</span> gene polymorphism -262 C&#47;T with bronchial asthma was determined using the Pearson <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test or Fisher&#39;s exact test&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">CAT</span> -262 C&#47;T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Healthy individuals &#40;n&#61;249&#41; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Asthmatic individuals &#40;n&#61;248&#41; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66&#46;7&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#46;4&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>C allele&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">81&#46;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">70&#46;9&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;51 &#40;0&#46;34&#8211;0&#46;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#46;0014&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>T allele&nbsp;\t\t\t\t\t\t\n
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                  """
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