Polymorphisms in HLA-DQB1 promoter and coding regions in Chinese Han patients with Vogt-Koyanagi-Harada syndrome
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF OCULAR FUNDUS DISEASES
- Issue:
- 5
- DOI:
- No doi available
- Key Word:
- 葡萄膜脑膜脑炎综合征/病因学;HLA抗原/生理学;聚合酶链反应;Uveomeningoencephalitic syndrome/etiology;HLA antigens/physiology;Polymerase chain reaction
Abstract： 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 phenol-chloroform method. Thirteen alleles were genotyped by polymerase chain reaction-sequence-specific primers (PCR-SSP), polymerase chain reactionsingle 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 Fisherexact 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-DQB1 * 0401 (0.318,44.00, P=0.000, OR=9.8). So was for HLA-DQB1*0303 (0.068 vs. 0.006, x2=9.67, P=0.002,OR=12.81). In contrast, the frequency of HLA-DQB1*0601 (0.017 vs. 0.096, x2=10.39, P=0.001,OR=0.16) and HLA-DQB1 * 0302 (0.062 vs. 0.193, x2=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, x2=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, x2=15.63, P=0.000). The frequency of combination of susceptible alleles in promoter and coding area (-189C and HLA-DQB1 * 0401) in VKH patients was statistically higher than that in controls, the frequency of combination of resistant alleles in control (-227G and HLA-DQB1 * 0601) was higher than that in VKH patients.Conclusions The specific interactions of SNP in the promoter and coding alleles of HLA-DQB1 are associated with the pathogenesis of VKH.
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