Evaluation of HLA-B*51 Subtypes in Behçet's Patients with Uveitis

Abstract

Aim: The HLA-B*51 allele has been determined to be the most important genetic factor in the pathogenesis of Behçet’s disease (BD). This relationship has been demonstrated in various ethnic groups and many studies have shown sequence alterations in B*51 protein coding regions. To date, 116 different subtypes of HLA-B*51 (HLA-B*51:01-B*51:122) have been identified (IMG/ HLA 3.5.0, June 14, 2011). This study investigated the distribution of B*51 subtypes in patients diagnosed with BD according to the 1990 International Study Group criteria and positive for B*51 compared to healthy controls. Material and Method: DNA was isolated from 40 unrelated B*51- positive BD patients and 54 healthy volunteer bone marrow donors. B*51 subtype analysis was done by polymerase chain reaction with sequence specific primers (PCR-SSP) (One Lambda Inc., CA, USA). Chi-square and Fisher’s exact tests were used in the statistical analysis (SPSS version 17.0). Results: There were no statistically significant associations between B*51 subtype and BD patients’ clinical characteristics or laboratory parameters (p<0.05). No significant difference was found between BD patients and controls in the frequency of B*51 subtypes. Conclusion: Although there has been much emphasis on the association between BD and the HLA*5101 subtype, which is a common finding in BD patients in the Turkish population and in other ethnic groups, the presence of this subtype at a comparable frequency in the control group indicates that the development of BD is not attributable to HLA*5101 alone. Our data suggest that in addition to genetic factors, certain environmental factors also play a role in the development of BD

Keywords

• Behçet’s disease,uveitis,allele,HLA-B*51,PCR-SSP

Behçet Üveitli Hastalarda HLA-B*51 Alt Tipinin Değerlendirilmesi

Abstract

Aim: The HLA-B*51 allele has been determined to be the most important genetic factor in the pathogenesis of Behçet’s disease (BD). This relationship has been demonstrated in various ethnic groups and many studies have shown sequence alterations in B*51 protein coding regions. To date, 116 different subtypes of HLA-B*51 (HLA-B*51:01-B*51:122) have been identified (IMG/ HLA 3.5.0, June 14, 2011). This study investigated the distribution of B*51 subtypes in patients diagnosed with BD according to the 1990 International Study Group criteria and positive for B*51 compared to healthy controls. Material and Method: DNA was isolated from 40 unrelated B*51- positive BD patients and 54 healthy volunteer bone marrow donors. B*51 subtype analysis was done by polymerase chain reaction with sequence specific primers (PCR-SSP) (One Lambda Inc., CA, USA). Chi-square and Fisher’s exact tests were used in the statistical analysis (SPSS version 17.0). Results: There were no statistically significant associations between B*51 subtype and BD patients’ clinical characteristics or laboratory parameters (p<0.05). No significant difference was found between BD patients and controls in the frequency of B*51 subtypes. Conclusion: Although there has been much emphasis on the association between BD and the HLA*5101 subtype, which is a common finding in BD patients in the Turkish population and in other ethnic groups, the presence of this subtype at a comparable frequency in the control group indicates that the development of BD is not attributable to HLA*5101 alone. Our data suggest that in addition to genetic factors, certain environmental factors also play a role in the development of BD

Keywords

• Behçet hastalığı,üveit,allel,HLA-B*51,PCR-SSP

References

1. 1. Sakane T, Takeno M, Suzuki N. Behçet’s disease. New Eng J Med, 1999;17:1284–1291.
2. 2. Öztaş P, Polat M, Gür G, et al. The etiopathogenesis of Behcet’s disease. Tr Klin J Dermatol 2006;16:181–5.
3. 3. Al-Otaibi LM, Porter SR, Poate TW. Behçet’s disease: a review. J Dent Res 2005;84.:209–22.
4. 4. Alpsoy E. Behçet Disease An Update in Ethiopathogenesis Tr J Dermatol 2013;7:41–5.
5. 5. Chang HK, Kim JU, Cheon KS, Chung HR. K. W. Lee5, I. H. Lee HLA-B51 and its allelic types in association with Behcet’s disease and recurrent aphthous stomatitis in Korea Clin Exp Rheumatol 2001;19/24:31–35.
6. 6. Gül A. Behcet’s disease: An update on the Pathogenesis. Clin Exp Rheumatol 22001;19/24:6–12. S6-S12.
7. 7. Kera J, Mizuki N, Ota M; Significant associations ofHLA-B*5101 and B*5108, and lack of association of classII alleles with Behcet’s disease in Italian patients. Tissue Antigens 1999;54(6):565–571.
8. 8. Paul M, Klein T, Krause I. Allelic distribution of HLAB*5 in HLA-B5-positive Israeli patients with Behcet’s disease. Tissue Antigens 2001;58(3):185–186.

9. 9. Gul A, Ohno S. HLA-B*51 and Behçet Disease Ocular Imminol inflame, 12/2011;20(1):37–43.
10. 10. Gonzalez-Escribano MF, Rodriguez MR, Walter K. Association of HLA-B51 subtypes and Behcet’s disease inSpain. Tissue Antigens 1998;52(1):78–80.
11. 11. Yabuki K, Ohno S, Mizuki N. HLA class I and II typing of the patients with Behcet’s disease in Saudi Arabia. Tissue Antigens 1999;54(3):273–277.
12. 12. Kotter I, Gunaydin I, Stubiger N. Comparative analysis of the association of HLA-B*51 suballeles with Behcet’s disease in patients of German and Turkish origin. Tissue Antigens 2001;58(3):166–170.
13. 13. Mizuki N, Ota M, Katsuyama Y. Sequencing-basedtyping of HLA-B*51 alleles and the significant associationof HLA-B*5101 and -B*5108 with Behcet’s disease in Greekpatients. Tissue Antigens 2002;59(2):118–121.
14. 14. Pirim I, Atasoy M, Ikbal M. HLA class I and class IIgenotyping in patients with Behcet’s disease: a regional study of eastern part of Turkey. Tissue Antigens, 2004;64(3):293–297.
15. 15. Gul A, Uyar FA, Inanc M, Ocal L, Barrett JH, Aral O. A weak association of HLA-B*2702 with Behcet’s disease. Genes Immune 2002;3:368–72.
16. 16. Petrushkin H, Hasan S, Stanford MR. Behçet’s disease: do natural killer cells play a significant role Front Immunol 2015;6:134.
17. 17. Kaya TJ. Genetics of Behçet’s Disease. Pathol Res Int 2012;6:1–6.
18. 18. Middleton D, Meenagh A, Sleator C. No association of KIR genes with Behcet’s disease. Tissue Antigens, 2007;70:435–438.
19. 19. Mizuki N, Ota M, Katsuyam Y, Yabuki K. Association analaysis between the MIC-A and HLA-B alleles in Japanase patients with Behçet’s disease. Arthr Rheumat 1999;42:1961–1966.
20. 20. Davatchi, F. Shahram, A. Nadji, S. Soroosh, A. R. Jamshidi, C. Chams, H. Chams, M Akbarian, . F. Gharibdoost, M. Acta Medica Iranica 2008;46(6):507–510.
21. 21. Kang EH, Kim JY, Takeuchi F. Associations between the HLA-A polymorphism and the clinical manifestations of Behcet’s disease. Arthritis Res Ther 2011;13(2):49.
22. 22. Akman A, Alpsoy E. Behcet’s Disease: Current Aspects in the Etiopathogenesis. Tr Dermato, 2009;43:2:32–8.
23. 23. Demirseren DD, Ceylan GG, Akoglu G. HLA-B51 subtypes in Turkish patients with Behçet’s disease and their correlation with clinical manifestations. Gen Mol Re, 2014;13(3):4788–4796.
24. 24. Suzuki KM, Suzuki N. Behçet’s disease. Clin Exp Med 2004;4:10–20.
25. 25. Azizlerli G, Kose AA, Sarica R, Gul A. Prevalence of Behçet’s disease in Istanbul, Turkey. Int. J Dermatol 2003;42:803–806.
26. 26. Varol A, Seifert O, Anderson CD. The skin pathergy test: innately useful. Arch Dermatol Res 2010;302:155–158.
27. 27. Maldini C, LaValley MP, Cheminant M. Relationships of HLA-B51 or B5 genotype with Behcet’s disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatol 2012;51:887–900.
28. 28. Pickering MC, Haskard DO. Behcet’s Syndrome. J Royal Coll Phys 2000;34(2):169–177.
29. 29. Evereklioglu C. Current concepts in the etiology and treatment of Behçet disease. Surv Ophthalmol 2005;50(4):297–350.
30. 30. Mizuki N, Inoko H, Ohno S. Pathogenic gene responsiblefor the predisposition of Behcet’s disease. Int Rev Immunol 1997;14:33 48.
31. 31. Takemoto Y, Naruse T, Namba K, Kitaichi N, Ota M, Shindo Y, Mizuki N, . Re-evaluation of heterogeneity in HLA-B*510101 associated with Behçet’s disease. Tissue Antigens 2008 72(4):347–53.
32. 32. Direskeneli H. Behçet’s disease: infectious aetiology, new autoantigens, and HLA-B51. Ann Rheum Dis 2001;60:996– 1002.