RESUMEN
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.
Asunto(s)
Antígenos HLA-DQ/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Síndrome Uveomeningoencefálico/genética , Adolescente , Adulto , Anciano , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Cadenas beta de HLA-DQ , Humanos , Masculino , Persona de Mediana Edad , Síndrome Uveomeningoencefálico/etnología , Síndrome Uveomeningoencefálico/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To investigate the frequency of HLA-DQB1 alleles in Chinese Han patients with Vogt-Koyanagi-Harada syndrome (VKH) and to analyze the relationships among the alleles and clinical manifestations. METHODS: Eighty-eight Chinese Han patients with VKH and 88 non-VKH normal controls were admitted. DNA was extracted from white blood cells of the subjects by phenol-chloroform method. Thirteen alleles were typed by polymerase chain reaction-sequence specific primer (PCR-SSP). Relationships among alleles and clinical features were analyzed. RESULTS: Twelve of thirteen already known HLA-DQB1 alleles were typed by PCR-SSP in patients with VKH. The most frequent allele in patients with VKH was HLA-DQB1*0401 (31.8%) and this was significantly higher than that of normal controls (31.8% vs. 4.6%, chi(2) = 44.00, P = 0.000, OR = 9.8, 95% CI 4.51 - 21.31). So was for HLA-DQB1*0303 (6.8% vs. 0.6%, chi(2) = 9.67, P = 0.002, OR = 12.81, 95% CI 1.65 - 99.58). On the contrary, the frequency of HLA-DQB1*0601 (1.7% vs. 9.7%, chi(2) = 10.39, P = 0.001, OR = 0.16, 95% CI 0.05 - 0.56) and HLA-DQB1*0302 (6.3% vs. 19.3%, chi(2) = 13.48, P = 0.000, OR = 0.28, 95% CI 0.14 - 0.57) in patients with VKH were significantly lower than that of normal controls. They found no statistical differences of clinical manifestations such as age of onset, visual acuity, cataract, complicated glaucoma, exudative retinal detachment between HLA-DQB1*0401 positive group and HLA-DQB1*0401 negative group in patients with VKH. CONCLUSIONS: (1) Alleles of HLA-DQB1*0401 and HLA-DQB1*0303 are susceptible to VKH. HLA-DQB1*0601 and HLA-DQB1*0302 are resistant to VKH. This is the first report that associates HLA-DQB1*0302 with resistant of VKH. (2) PCR-SSP is a rapid method for typing the HLA-DQB1 alleles and can be used routinely.