Objective To investigate the genetic interaction of HLA-DQB1 promoter and coding alleles in the pathogenesis of Vogt-Koyanagi-Harada syndrome (VKH). Methods Eighty-eight Chinese Han patients with VKH and eighty-eight non-VKH normal controls were enrolled in this study. DNA was extracted from white blood cells of the subjects by phenolchloroform method. Thirteen alleles were genotyped by polymerase chain reaction-sequence-specific primers (PCR-SSP), polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and clone-sequencing was applied to determine the polymorphisms of the promoter and coding regions of HLA-DQB1 gene. Chromas and Bioedit software were used to analyze the sequences of the promoter of HLA-DQB1. Chi-square test and Fisher exact test were the statistical methods. Relationships among single nucleotide polymorphism (SNP) in the promoter and coding region were analyzed. Results Twelve of thirteen already known HLA-DQB1 alleles were genotyped by PCR-SSP in VKH patients. The most frequent allele in VKH patients was HLA-DQB10401 (0.318, 56∶176) which was significantly higher in patients than that in normal controls (0.045, 8∶176) ( chi;2＝44.00, P＝0.000, OR＝9.8). So was for HLA-DQB10303 (0.068 vs. 0.006, chi;2＝9.67, P＝0.002, OR＝12.81). In contrast, the frequency of HLA-DQB10601 (0.017 vs.0.096, chi;2＝10.39, P＝0.001, OR＝0.16) and HLA-DQB10302 (0.062 vs. 0.193, chi;2＝13.48, P＝0.000, OR＝0.28) in VKH patients were significantly lower than normal controls. Twelve SNP were found in all subjects. The frequency of C allele at position -189C/A in VKH patients was significantly higher than that in controls (0.324 vs. 0.074, chi;2＝45.92, P＝0.000). However, the frequency of G allele at position -227G/A in VKH patients was significantly lower than that in the normal controls (0.011 vs. 0.108, chi;2＝15.63,P＝0.000). The frequency of combination of susceptible alleles in promoter and coding area （-189C and HLA-DQB10401） in VKH patients was statistically higher than that in controls, the frequency of combination of resistant alleles in control (-227G and HLA-DQB10601) was higher than that in VKH patients. Conclusion s The specific interactions of SNP in the promoter and coding alleles of HLA-DQB1 are associated with the pathogenesis of VKH.
Citation： 闵寒毅,刘英,牛妮芳,张美芬,朱席琳,赵家良. Polymorphisms in HLA-DQB1 promoter and coding regions in Chinese Han patients with Vogt-Koyanagi-Harada syndrome. Chinese Journal of Ocular Fundus Diseases, 2010, 26(5): 418-422. doi: Copy