DNA TYPING OF HLA CLASS-II GENES - DRB1(ASTERISK)0803 INCREASES THE SUSCEPTIBILITY OF JAPANESE TO PRIMARY BILIARY-CIRRHOSIS

The association between human leukocyte antigens and primary biliary cirrhosis is controversial, but major histocompatibility complex class II antigen DR8 was recently reported to be associated with increased susceptibility for primary biliary cirrhosis in some Caucasians and Japanese. Accordingly, we performed DNA typing of HLA class II genes in Japanese patients with primary biliary cirrhosis. The genotypes of HLA DRB1, DRB3-5, DQA and DQB were determined by polymerase chain reaction and subsequent hybridization with sequence specific oligoncleotides in 31 primary biliary cirrhosis patients and 215 racially matched local controls. DR8 was found in 24 of the 31 primary biliary cirrhosis patients and was highly concentrated in DRB1*0803. The gene frequency of DRB1*0803 was significantly increased in the patients (35.5% vs 7.4%, relative risk=6.84, p<0.0001). DQA1*0103 and DQB1*0601 were also increased in the primary biliary cirrhosis patients, in relation to linkage disequilibrium with DRB1*0803 on the same haplotype. In contrast, DQA1*0102 showed a significantly lower frequency in the primary biliary cirrhosis patients (p<0.05). These data suggest that DRB1* 0803 is one of the HLA class II genes related to an increased risk of primary biliary cirrhosis in Japanese individuals. (C) Journal of Hepatology.