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Vol. 40. Issue 10.
Pages 449-452 (October 2004)
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Vol. 40. Issue 10.
Pages 449-452 (October 2004)
Original Articles
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Human Leukocyte Antigens A and B in Turkish Patients With Sarcoidosis
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G. Çelika,
Corresponding author
celik@medicine.ankara.edu.tr

Correspondence: Assoc. Prof G. Çelik. Kazakistan cad. 102/14 Emek, 06510. Ankara. Turkey
, E. Şena, A.F. Ülgera, Ö. Özdemir-Kumbasara, D. Alpera, A.H. Elhanb, H. Tutkakc, A. Çetinyürekb
a Department of Pulmonary Disease and Tuberculosis, School of Medicine, Ankara University, Ankara, Turkey
b Department of Biostatistics, School of Medicine, Ankara University, Ankara, Turkey
c Department of Immunology, School of Medicine, Ankara University, Ankara, Turkey
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Objective

Associations between human leukocyte antigens (HLA) and sarcoidosis have been reported in several studies. We aimed to investigate these associations in Turkish patients.

Patients and Method

We performed HLA-A, HLA-B, HLA-C, and HLA-D typing in 83 patients with sarcoidosis and in 250 healthy controls using a microlymphocytotoxicity method to investigate genetic susceptibility to the disease.

Results

Because of significant violation of Hardy-Weinberg equilibrium at HLA-C and HLA-DQB1 loci, only results obtained at other HLA loci were used. Although HLA-A9, HLA-B5, and HLA-B8 allele frequencies were significantly higher in the patient group compared to the controls (odds ratio [OR]= 21.8, P = .015; OR=9.34, P = .049; OR=2.26, P = .031, respectively), none of the differences remained significant after applying the Bonferroni correction. HLA-A24, HLA-A26, and HLA-B62 alleles were significantly less frequent in the patient group compared to the controls (OR=0.48, P = .018; OR=0.19, P = .003; OR= 0.11, P = .044, respectively). However, the differences also failed to remain significant after Bonferroni correction.

Conclusions

These results suggest that both HLA may play significant roles (either increasing or reducing risk) in the pathogenesis of sarcoidosis and in its distinct clinical forms and laboratory findings.

Key Words:
Human leukocyte antigens
Sarcoidosis
Turkish patients
Objetivo

En varios estudios se ha demostrado la existen-cia de asociaciones entre los antígenos leucocitarios humanos (HLA) y la sarcoidosis. El objetivo de nuestro estudio ha sido la investigación de estas asociaciones en pacientes turcos.

Pacientes Y Método

Se ha realizado la tipificación HLA-A, HLA-B, HLA-C y HLA-C en 83 pacientes con sarcoidosis y en 250 controles sanos mediante un método de microlinfo-citotoxicidad, con objeto de determinar la susceptibilidad frente a la enfermedad.

Resultados

Debido a la importante violación del equili-brio de Hardy-Weinberg en los loci HLA-C y HLA-DQB1, sólo se utilizaron los resultados obtenidos en los demás loci HLA. Aunque las frecuencias de los alelos HLA-A9, HLA-B5 y HLA-B8 fueron significativamente mayores en el gru-po de pacientes que en el grupo control (cociente de posibili-dades [CP] = 21,8, p = 0,015; CP = 9,34, p = 0,049; CP = 2,26, p = 0,031, respectivamente), ninguna de estas diferen-cias mantuvo la significación estadística tras la aplicación de la corrección de Bonferroni. Los alelos HLA-A24, HLA-A26 y HLA-B62 fueron significativamente menos frecuentes en el grupo de pacientes que en el grupo de controles (CP = 0,48, p = 0,018; CP = 0,19, p = 0,003; CP = 0,11, p = 0,044, respectivamente). Sin embargo, las diferencias tampoco fueron estadísticamente significativas después de la corrección de Bonferroni.

Conclusiones

Estos resultados indican que los HLA pueden desempeñar una función significativa (con aumento o reducción del riesgo) en la patogenia de la sarcoidosis, así como en sus diferentes formas clínicas y en sus alteraciones analíticas.

Palabras clave:
Antígenos HLA
Sarcoidosis
Pacientes turcos
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REFERENCES
[1]
K Bogunia-Kubik, J Tomeczko, K Suchnicki, A Lange.
HLADRB1*03, DRB1*11 or DRB1*12 and their respective DRB3 specificities in clinical variants of sarcoidosis.
Tissue Antigens, 57 (2001), pp. 87-90
[2]
M Berlin, A Fogdell-Hahn, O Olerup, A Eklund, J Grunewald.
HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis.
Am J Respir Crit Care Med, 156 (1997), pp. 1601-1605
[3]
M Ishihare, S Ohno.
Genetic influences on sarcoidosis.
Eye, 11 (1997), pp. 155-161
[4]
H Kunikane, S Abe, Y Tsuneta, T Nakayama, Y Tajima, J Misonou, et al.
Role of HLA-DR antigens in Japanese patients with sarcoidosis.
Am Rev Respir Dis, 135 (1987), pp. 688-691
[5]
BA Rybicki, MJ Maliarik, M Major, J Popovich Jr, MC Iannuzzi.
Genetics of sarcoidosis.
Clin Chest Med, 18 (1997), pp. 707-717
[6]
E Hedfords, F Lindström.
HLA-B8/DR3 in sarcoidosis.
Tissue Antigens, 22 (1983), pp. 200-203
[7]
N Odum, N Milman, BK Jakobsen, J Georgsen, A Svejgaard.
HLA class II (DR, DQ, DP) in patients with sarcoidosis: evidence of an increased frequency of DRw6.
Exp Clin Immunogenet, 8 (1991), pp. 227-232
[8]
D Nowack, KM Goebel.
Genetic aspects of sarcoidosis.
Arch Intern Med, 147 (1987), pp. 481-483
[9]
M Martinetti, C Tinelli, V Kolek, M Cuccia, L Salvaneschi, L Pasturenzi, et al.
“The sarcoidosis map:” a joint survey of clinical and immunogenetic findings in two European countries.
Am J Respir Crit Care Med, 152 (1995), pp. 557-564
[10]
DJ Evans, RJ Shaw.
Genetic factors.
Sarcoidosis and other granulomatous disorders. Lung biology in health and disease, pp. 205-211
[11]
F Yorulmaz, T Cadlar, C Erel, M Ozaydin.
Prevalance and annual risk of tuberculosis infection in Edirne.
Scand J Infect Dis, 34 (2002), pp. 654-656
[12]
PI Terasaki, D Bernoco, MS Park, G Ozturk, Y Iwaki.
Microdroplet testing for HLA-A, -B, -C, and -D antigens.
Am J Clin Pathol, 69 (1978), pp. 103-120
[13]
JL Fleiss.
Statistical methods for rates and proportions, 2nd ed., pp. 61-64
[14]
M Nei.
Analysis of gene diversity in subdivided populations.
Proc Natl Acad Sci USA, 70 (1973), pp. 3321-3323
[15]
M Nei, F Tajima, Y Tateno.
Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data.
J Mol Evol, 19 (1983), pp. 153-170
[16]
M Luisetti, A Beretta, L Casali.
Genetic aspects in sarcoidosis.
Eur Respir J, 16 (2000), pp. 768-780
[17]
DA Brewerton, C Cockburn, DC James, DG James, E Neville.
HLA antigens in sarcoidosis.
Clin Exp Immunol, 27 (1977), pp. 227-229
[18]
SA Olenchock, E Hise, J Marx.
HLA-B8 in sarcoidosis.
Ann Allergy, 47 (1981), pp. 151-153
[19]
K Lenhart, V Kolek, A Bartova.
HLA antigens associated with sarcoidosis.
Dis Markers, 8 (1990), pp. 23-29
[20]
Y Ina, K Takada, M Yamamoto, M Morishita, Y Senda, Y Torii.
HLA and sarcoidosis in the Japanese.
Chest, 95 (1989), pp. 1257-1261
[21]
H Kunikane, S Abe, E Yamaguchi, JM Aparico, A Wakisaka, T Yoshiki, et al.
Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis.
Thorax, 49 (1994), pp. 573-576
[22]
J Gardner, HG Kennedy, A Hamblin, E Jones.
HLA association in sarcoidosis: a study of two ethnic groups.
Thorax, 39 (1984), pp. 19-22
[23]
E Hedfors, E Möller.
HLA antigens in sarcoidosis.
Tissue Antigens, 3 (1972), pp. 95-98
[24]
H Sato, JC Grutters, P Pantelidis, AN Mizzon, T Ahmad, AJ van Houte, et al.
HLA-QB1*0201, a marker for good prognosis in British and Dutch patients with sarcoidosis.
Am J Respir Cell Mol Biol, 27 (2002), pp. 406-412
[25]
SK Sharma, A Balamurugan, RM Pandey, PK Saha, NK Mehra.
Human leukocyte antigen-DR alleles influence the clinical course of pulmonary sarcoidosis in Asian Indians.
Am J Respir Cell Mol Biol, 29 (2003), pp. 225-231
[26]
MD Rossman, B Thompson, M Frederick, M Maliarik, MC Iannuzzi, BA Rybicki, et al.
HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites.
Am J Hum Genet, 73 (2003), pp. 720-735
[27]
MC Iannuzzi, MJ Maliarik, LM Poisson, BA Rybicki.
Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans.
Am J Respir Crit Care Med, 167 (2003), pp. 1225-1231
[28]
Uyar FA, Dorak MT, Saruhan-Direskeneli G. HLA-A, -B, -C alleles, and HLA haplotypes in Turkey: relationship to other populations tissue [in press]. Antigens 2004.
[29]
G Akokan, S Celikoglu, F Göksel, Sl Demirci.
Antigens in Turkish patients with sarcoidosis.
N Engl J Med, 296 (1977), pp. 759
[30]
A Arnaiz-Villena, M Karin, N Bendikuze, EG Casado, J Moscoso, C Silvera, et al.
HLA alleles and haplotypes in the Turkish population: relatedness to Kurds, Armenians and other Mediterraneans.
Tissue Antigens, 57 (2001), pp. 308-317
[31]
A Dubanewicz, Z Szczerkowska, A Hoppe.
Comparative analysis of HLA class I antigens in pulmonary sarcoidosis and tuberculosis in the same ethnic group.
Mayo Clin Proc, 78 (2003), pp. 436-442
[32]
I Persson, LP Ryder, LS Nielsen, A Svejgaard.
The HLA-A7 histocompatibility antigen in sarcoidosis in relation to tuberculin sensitivity.
Tissue Antigens, 6 (1975), pp. 50-53
[33]
MJ Smith, CWG Turton, DN Mitchell, M Turner-Warwick, LM Morris, SD Lowler.
Association of HLA-B8 with spontaneous resolution in sarcoidosis.
Thorax, 36 (1981), pp. 296-298
[34]
GH Guyatt, WG Bensen, LP Stolmon, L Fagnilli, DP Singal.
HLA-B8 and erythema nodosum.
Can Med Assoc J, 127 (1982), pp. 1005-1006
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