Human leukocyte antigen-C genes and susceptibility to primary sclerosing cholangitis.
Genetic susceptibility to primary sclerosing cholangitis (PSC) is associated with the extended HLA A1-B8-DR3 haplotype and also with the DRB3*0101-DRB1*0301-DQA1*0103-DQB1*0603 haplotype. However, very few studies have considered the role of HLA C which lies between HLA A and B, is highly polymorphic, and encodes proteins which play an important role in immunoregulation and in disease susceptibility. Traditional assignment of HLA Cw antigens by serology is both inaccurate and unreliable, with a high error rate. The aim of this study was to characterize the distribution of HLA C alleles in a large group of patients with primary sclerosing cholangitis by using a recently developed polymerase chain reaction-based genotyping technique. Ninety-three white adult patients of northern European origin with well characterized PSC and 100 geographically and racially matched controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction-based genotyping, HLA A and B antigens by standard microlymphocytotoxicity test and extended haplotypes were constructed according to known patterns of linkage disequilibrium. The Cw*07 gene was found in 67.7% of patients versus 54% of controls (P = .051, OR = 1.79). This increase was a result of inheritance of the Cw*0701 allele which was found in 51.6% of patients 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 Cw*07 group: Cw*0702, Cw*0703, and Cw*0704. HLA-encoded genetic susceptibility to PSC is associated with the HLA Cw*0701 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 sclerosing cholangitis lies close to the HLA C locus.
Moloney
M M
MM
Institute of Liver Studies, King's College School of Medicine and Denistry, London, UK.
Thomson
L J
LJ
Strettell
M J
MJ
Williams
R
R
Donaldson
P T
PT
D000483:Alleles; D015209:Cholangitis, Sclerosing / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D015236:HLA-C Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology
D015236:HLA-C Antigens; D006684:HLA-DR Antigens