In studies to date seeking associations between human leukocyte antigens (HLA) and primary biliary cirrhosis, no class I association but several different class II associations have been described. The aims of this study were to reassess the DR associations in primary biliary cirrhosis and to examine for the first time the role of DQB. DRB genotypes were determined on standard Taq1 restriction-fragment-length polymorphism analysis in 159 white northern European patients with the disease and 162 racially matched local controls. Polymerase chain reaction gene amplification and sequence-specific oligonucleotide analysis were used to determine DQB genotypes in 89 patients and 181 controls. An increased frequency of human leukocyte antigen DR8 was observed in the patient group (11% vs 4%; relative risk = 3.3; p < 0.01). Although we saw an increased frequency of the DQB1*0402 allele (11% vs. 3%; relative risk = 3.5; p < 0.025), this was not significant after correction for multiple testing. The strongest association was with the two-locus haplotype DR8-DQB1*0402 (11% vs. 2.2%; relative risk 5.5; p < 0.001). The DRB data reported here confirm the findings of previous studies, although the described association with DR8 is considerably weaker. The weak genetic contribution of human leukocyte antigen in the susceptibility to primary biliary cirrhosis is in contrast to its role in other autoimmune liver diseases.
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