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High concordance rate in monozygotic twins and familial clustering of patients with primary biliary cirrhosis (PBC) indicate the involvement of strong genetic factors in the development of PBC. To identify susceptibility loci for PBC in Japanese population, a genome-wide association study (GWAS) and subsequent replication study were performed in a total of 1327 PBC cases and 1120 healthy controls. Two significant (p<5x10) non-HLA susceptibility loci (TNFSF15 and POU2AF1) for PBC were identified. In addition, 10 loci (CD80, IKZF3, IL7R, NFKB1, STAT4, CXCR5, TNFAIP2, MAP3K7IP1, rs6974491, DENND1B) out of 21 non-HLA susceptibility loci for PBC which were recently identified in European descent showed significant associations in Japanese population. These results indicated the importance of two disease-pathways in both European descent and Japanese population, Th1/Th17 differentiation of T cells (CD80, IL12A, IL12RB2, STAT4, TNFSF15) and B cell differentiation to plasma cells (IL7R, CXCR5, POU2AF1, SPIB, IKZF3), although there are some ethnic differences in disease-susceptibility loci for PBC. In addition, the study for systemic and local expression of TNF-like ligand 1A (TL1A), which is encoded by TNFSF15, indicated that TL1A may be involved in the pathogenesis of PBC. Rec.1/17/2014, Acc.3/7/2014, pp78-86

Analysis of disease-pathways by susceptibility genes in primary biliary cirrhosis