Objective: To investigate the single nucleotide polymorphism of the promoter of HLA-DQB1(QBP) in Chinese Han patients with Vogt-Koyanagi-Harada syndrome.
Methods: Case-control design was applied. Eighty-eight Chinese Han patients with Vogt-Koyanagi-Harada syndrome and 88 non-Vogt-Koyanagi-Harada syndrome controls were admitted. DNA was extracted from the peripheral white blood cells of the subjects by the phenol-chloroform method. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and clone-sequencing were applied to determine the sequences of the promoter of HLA-DQB1. Chromans and Bioedit software were used to analyze the sequences of the promoter of HLA-DQB1. Chi-square test and Fisher exact test were applied to compare the frequencies of bands of QBPs and SNPs for the two groups.
Results: Sixteen band patterns of HLA-QBP were shown by polyacrylamide gel electrophoresis (PAGE). The band frequencies of QBPb (corresponding gene sequence was QBP2.1 + 77C > A, chi2 = 26.01, Pc < 0.001) and QBPl (corresponding gene sequence was QBP3.3, chi2 = 16.99, Pc < 0.001) were significantly higher in patients with Vogt-Koyanagi-Harada syndrome than that in normal controls (Pc < 0.001). However, the frequencies of QBPg (corresponding gene sequence was QBP3.1, chi2 = 12.10, Pc < 0.05) and QBPn (corresponding gene sequence was QBP6.1 + 39G > A, chi2 = 14.64, Pc < 0.05) were significantly lower in patients with Vogt-Koyanagi-Harada syndrome than those of the controls. Twelve SNPs were found in all subjects. The frequency of C allele at position -189C/A in patients with Vogt-Koyanagi-Harada syndrome was significantly higher than that in controls (chi2 = 45.92, P = 0.000). However, the frequency of G allele at position -227G/A in patients with Vogt-Koyanagi-Harada syndrome was significantly lower as compared with that in the normal controls (chi2 = 15.63, P = 0.000).
Conclusions: C allele of -189C/A is a genetically susceptible factor of Vogt-Koyanagi-Harada syndrome and G allele of -227G/A is the protective factor of Vogt-Koyanagi-Harada syndrome.