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HLA class II molecules confer both susceptibility and progression in Japanese pa源自：Hepatology
Abstract
Along with twin and family studies, recent genome-wide association studies suggest that genetic factors contribute to the susceptibility and severity of primary biliary cirrhosis (PBC). Although several reports have demonstrated that the HLA DRB1*08:03 allele is associated with disease susceptibility in Japan, the precise analysis of HLA haplotypes and the role of amino acid alignment have not been fully clarified. We investigated HLA class I A, B, and C and HLA class II DRB1 and DQB1 alleles and haplotypes in 229 Japanese patients with PBC and compared them with the published data of 523 healthy subjects. Significant associations were found with PBC susceptibility for the DRB1*08:03-DQB1*06:01 haplotype [13% vs. 6%, P = 0.000025; odds ratio (OR) = 2.22] and DRB1*04:05-DQB1*04:01 haplotype (17% vs. 13%, P = 0.044; OR = 1.38). Conversely, there were significant protective associations with the DRB1*13:02-DQB1*06:04 haplotype (2% vs. 5%, P = 0.00093; OR = 0.27) and DRB1*11:01-DQB1*03:01 haplotype (1% vs. 4%, P = 0.03; OR = 0.37). The frequency of the DRB1*09:01-DQB1*03:03 haplotype was significantly higher in patients who had received orthotopic liver transplantation (OLT) (33% vs. 11%, P = 0.0012; OR = 3.96). Furthermore, the frequency of serine at position 57 (P = 0.0000015; OR = 1.83) of the DRβ?chain differed the most in patients with PBC compared with healthy subjects. Conclusion: This study established the role of HLA haplotypes in determining PBC susceptibility and progression in the Japanese population. Further re-sequencing of the HLA region is required to more precisely identify the genetic components of PBC.