Human leukocyte antigens in Japanese patients with biliary atresia: Retrospective analysis of patients who underwent living donor liver transplantation

Biliary atresia (BA) is a neonatal obstructive cholangiopathy characterized by a fibrosclerosing obliteration of the extrahepatic bile duct. The aim of this study was to investigate the relationship between human leukocyte antigens (HLA) and susceptibility to BA. We retrospectively analyzed 392 Japanese patients with BA and without extrahepatic anomalies who underwent living donor liver transplantations at our institute. Healthy Japanese volunteers (n = 828) served as normal controls. A significant positive association was observed between BA and HLA-DR2 (39.0% of patients vs. 30.4% of controls, odds ratio = 1.46, p = 0.029). Two-locus analyses disclosed that DR2 was not independently associated with BA, but the increased frequency of HLA-A24 and -B52 reflected the linkage disequilibrium between -A24, -B52, and -DR2. Moreover, the frequency of the haplotype HLA-A24-B52-DR2 was significantly higher in patients with BA than in the general Japanese populations described in the literature (odds ratio = 2.20, p = 0.00124). These results indicate that the gene for BA susceptibility is in close linkage disequilibrium with the HLA-A24-B52-DR2 haplotype observed in the Japanese population. We speculate that a gene at the locus close to HLA plays an important role in the pathogenesis of BA.