HLA-DQA1 And DQB1 Alleles Are Associated With Genetic Susceptibility To Vitiligo In Chinese Hans

Background: Vitiligo is acquired hypomelanotic disorder, usually beginning in childhood or young adulthood. The prevalence of the disease is 0.1%~2% in Chinese, without preference for gender. Up to now, the pathogenesis of vitiligo remains obscure, such as the genetic, autoimmune, neural, and melanocyte self-destruction hypotheses. The inherited nature of vitiligo and its frequent association with autoimmune diseases have prompted studies on the association between HLA and vitiligo. Studies have shown that the association of HLA with vitiligo varies among different ethnic groups. Recently, by using linkage disequilibrium analysis of HLA markers in familial vitiligo, it has been demonstrated that a major determinant of vitiligo could be located at 6p21.3-21.4 spanning the HLA. During the past decade years, the frequencies of HLA-A2, A3, A10, A30+31, B13, B15 antigens have significantly increased and the frequencies of HLA-A28, B46 antigens have decreased highly in patients with vitiligo in Chinese Hans. The frequencies of HLA-DRBl*070x, DRB1* 1201,2 alleles have been reported to increase significantly and the frequencies HLA-DRBl*0301,2 allele have decreased highly in patients with vitiligo in Northern Chinese Hans. Objective: To perform genotyping of HLA-DQA1 and DQB1 on Chinese Hans vitiligo population in order to identify susceptible and protective HLA alleles in vitiligo. Methods: Polymerase chain reaction sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles among 187 patients with vitiligo and 273 healthy controls.Results: (1)The frequencies of HLA-DQA1*0302 (22.73% vs. 18.84%, OR=1.98, Pc<0.01), DQB1*0303 (28.07% vs. 14.47%, OR=3.14, Pc<0.001), DQBl*0503 (6.68% vs. 2.20%, OR=3.36,Pc<0.05) alleles were significantly increased in patientswith vitiligo compared with the controls, and HLA-DQA1*0501 (7.49% vs. 15.20%, OR=0.40, Pc<0.01) allele frequency was highly decreased. (2) HLA-DQA1*0302 (34. 31% vs. 14. 84%,OR=5.19,Pc<0.001), DQA1*0601 (13. 73% vs. 5. 68%, OR=2.95, Pc<0.05), DQB 1*0303 (32. 35% vs. 14.47%, OR=4.50, Pc<0.001), DQB 1*0503 (11.76% vs. 2.20%, OR=6.69, Pc<0.001) alleles were positively associated, whereas HLA-DQA 1*0501 (0.98% vs. 15.20%, OR=0.05, PcO.001) allele was negatively associated with childhood vitiligo patients, and HLA-DQB1*0303 (26. 47% vs. 14.47%, 0R=2.76, OR=2.76, Pc<0.001) allele was positively associated with adult vitiligo patients, compared with the controls. ㏕he frequency of HLA-DQB 1*0303 (30.11% vs. 14.47%, OR=3.72, PcO.001) allele was significantly increased in localized vitiligo patients vs. the controls, whereas HLA-DQAl*0302 (25. 53%vs. 14. 84%, OR=2.47, PcO.01), DQB1*0303 (25. 53% vs.14. 47%, OR=2.67, PcO.01), DQBl*0503 (8.51% vs. 2.20%, 0R=4. 46, OR=4.46, Pc<0.01) alleles frequencies were significantly increased and DQAl*0501 (5. 32% vs.15. 20%, OR=0.27, PcO.01) allele frequency was highly decreased in generalized vitiligo patients.Conclusions: HLA-DQA1*O3O2, DQAl*0601, DQB1*O3O3 and DQB1*O5O3 alleles could be susceptible alleles of vitiligo, while HLA-DQAl*0501 allele could be protective allele in Chinese Hans. There may be different genetic backgrounds between vitiligo patients of childhood and adult, localized and generalized.