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Susceptibility to primary biliary cirrhosis is associated with human leukocyte antigen DRB1*0803 in Japanese patients

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Abstract

An association of primary biliary cirrhosis (PBC) with human leukocyte antigen (HLA) class II has been reported in previous studies based on the results of serological HLA typing. To evaluate the association between PBC and HLA class II more precisely, we performed HLA-DRB1 and DPB1 genotyping in 53 Japanese patients with PBC using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In DRB1 genotyping, the frequency of the*0803 allele was significantly higher in patients with PBC than that in control subjects. Twenty out of 53 patients were*0803 positive (37.7%), whereas only five out of 60 controls (8.3%) had the allele (relative risk = 6.67;P < 0.001; correctedP < 0.05). In DPB1 genotyping, there was no significant difference in the frequency of the DPB1 alleles between patients with PBC and controls. Amino acid analysis of the DRβ chain revealed that the frequency of leucine at position 74 was significantly higher in patients with PBC than that in controls. These results suggest that HLA-DRB1*0803 allele and a subsequent amino acid substitution encoded by the polymorphic regions of the allele may play an important role in the pathogenesis of PBC.

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