Association Analysis Of Liver Cirrhosis Induced By Hepatitis B Virus And Class Ⅰ HLA Genes

Objective: To investigate the association between liver cirrhosis induced by HBV and the polymorphisms of HLA-A loci in Fujian province Han population and to screen HLA predisposing genes related with hepatic fibrosis by HBV.Methods: The technique of sequencing-based typing was adopted in molecularly genotyping HLA-A alleles in unrelated individuals with liver cirrhosis induced by HBV and matched controls who healthy, all of the subjects were collected from a Chinese Han population in Fujian province. The distribution of alleles in control group was checked for deviations from Hardy-Weinberg equilibrium with genetic software. Associations between disease phenotype and frequencies of alleles, HLA genotypes, haplotype were statistically analyzed by Pearson x2 test, Trend test, Multinomial conditional logistic regression and so on to screen the HLA predisposing genes related with liver cirrhosis induced by HBV.Result: (1) For the total subjects, 12Groups and 26 Alleles were successfully detected in HLA-A. HLA-A,DRB1 meet the Hardy-Weinberg equilibrium for distribution of alleles in control group. (2)It was found by single factor correlation analysis that significant differences were observed in the allele frequencies of HLA-A*2402 between patients group and control group. (3) It was indicated by non-conditional logistic regression analysis that significant differences were observed in the allele frequencies of HLA-A*2402 between patients group and control group. (4)It was showed by non-conditional logistic regression analysis that significant differences were observed in the genotype frequencies of HLA-A2402,HLA-A0201 between patients group and control group.(5) It was demonstrated by genotype dose-response relationship analysis that there was significant dose-response relationship of the association between liver cirrhosis induced by HBV and the genotype HLA-A2402 .Conclusion: (1) The allele and genotype of HLA-A*2402 is positively associated with liver cirrhosis induced by HBV in Han population. (2) Compared with the HBV antigen epitopes presented by other HLA loci, the HBV antigen epitopes presented by HLA- A*2402 are more likely to give rise to stronger immune response, which induced persistant liver injure and hepatic fibrsis..