HUMAN-LEUKOCYTE ANTIGEN-C GENES AND SUSCEPTIBILITY TO PRIMARY SCLEROSING CHOLANGITIS

Genetic susceptibility to primary sclerosing cholangitis (PSC) is asso ciated with the extended HLA A1-B8-DR3 haplotype and also with the DRB 30101-DRB1*0301-DQA1*0103-DQB1*0603 haplotype. However, very few stud ies have considered the role of HLA C which lies between HLA A and B, is highly polymorphic, and encodes proteins which play an important ro le in immunoregulation and in disease susceptibility Traditional assig nment of HLA Cw antigens by serology is both inaccurate and unreliable , with a high error rate. The aim of this study was to characterize th e distribution of HLA C alleles in a large group of patients with prim ary sclerosing cholangitis by using a recently developed polymerase ch ain reaction-based genotyping technique, Ninety-three white adult pati ents of northern European origin with well characterized PSC and 100 g eographically and racially matched controls were studied. HLA C and HL A DRB1 alleles were assigned by polymerase chain reaction-based genoty ping, HLA A and B antigens by standard microlymphocytotoxicity test an d extended haplotypes were constructed according to known patterns of linkage disequilibrium. The Cw07 gene was found in 67.7% of patients versus 54% of controls (P = .051, OR = 1.79), This increase was a resu lt of inheritance of the Cw0701 allele which was found in 51.6% of pa tients compared with 34% of controls (P = .013, OR = 2.07). There were no significant differences in the frequencies of any of the other Cw alleles including the Cw07 group: Cw*0702, Cw*0703, and Cw*0704. HLA- encoded genetic susceptibility to PSC is associated with the HLA Cw07 01 allele, but the association is weak and may simply reflect linkage disequilibrium with the HLA B8-DR3 haplotype, These findings indicate that the telomeric limit of HLA-encoded susceptibility to primary scle rosing cholangitis lies close to the HLA C locus.