Susceptibility to autoimmune hepatitis (AIH) is associated extend these observations, concentrating within the HLA class II region. Studies thus far have identified associations with the HLA A1-B8-DR3 haplotype, DR4 antigen, and, more specifically, the HLA DRB3*0101, DRB1*0301, and with the DRB3*0101, DRB1*0301, and DRB1*0401 alleles, which encode the HLA antigens, DR52a, DR3, and DR4, DRB1*0401 alleles. Few investigators, however, have examined the HLA C locus in AIH, which warrants detailed study respectively, 4,5 but the class I loci have been largely overlooked. Early studies suggested that the association with HLA in view of its recently described roles in immunoregulation. Eighty-seven adult, white patients with well-characterized A1 was weak, but there was a strong association with B8, which in relative terms may be comparable with or even type 1 AIH and 100 controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction greater than that reported for DR3. 6,7 To date, only two studies 8,9 have examined the contribution of HLA C in AIH. In (PCR)-based genotyping. HLA A and B antigens were determined by standard microlymphocytotoxicity assay. Ex-1981, Lepage et al.8 studied 55 patients with chronic active hepatitis and identified HLA Cw7 as being more significantly tended haplotypes were constructed according to known patterns of linkage disequilibrium. Only one HLA C locus associated with AIH than either HLA DR3 or B8. Although the statistical foundation of Lepage's study, which included allele, Cw*0701, which was present in 54% of patients versus 34% of controls (P Å .006; relative risk [RR] Å patients with hepatitis B virus infection, is uncertain and the second study was based on only six patients, 9 there are 1.54) was associated with AIH. The overall increase in the frequency of the Cw*07 gene (70.1% of patients vs. 54% autoimmune diseases in which the primary HLA association is with the C locus.10 of controls; P Å .024; RR Å 1.3) was due entirely to inheritance of the Cw*0701 allele rather than the other Cw*07Investigations seeking disease associations with HLA C have lagged behind studies of HLA A and B and the class II alleles, Cw*0702, *0703, and *0704. The RR for Cw*0701 (RR Å 1.54) is greater than that for HLA A1 (RR Å 1.33) loci DR, DQ, and DP. This is mainly because of difficulty in assigning HLA C antigens by serological methods. Thus, at and DRB1*0301 (RR Å 1.49), but less than that for HLA-B8 (RR Å 1.75). The present findings suggest that the gene least 20% of white individuals test blank for one HLA C allele, 11,12 10% of Cw antigens may be falsely assigned, and or genes conferring susceptibility to AIH lie in the region centromeric to the HLA A locus between HLA C and DRB1. approximately 30% of sequenced alleles are undetectable by serology. 13 The development of PCR-based genotyping has Although linkage disequilibrium with both B8 and DRB1*0301 may account for our finding of an increased largely eliminated these problems, and, with the recently described rol...
