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Amino acid substitutions at position 38 of the DRβ polypeptide confer susceptibility to and protection from primary sclerosing cholangitis
Author(s) -
Farrant J. Mark,
Doherty Derek G.,
Donaldson Peter T.,
Vaughan Robert W.,
Hayllar Karen M.,
Welsh Ken I.,
Eddleston Adrian L. W. F.,
Williams Roger
Publication year - 1992
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840160217
Subject(s) - primary sclerosing cholangitis , primary (astronomy) , position (finance) , amino acid substitution , amino acid , medicine , gastroenterology , biology , genetics , mutation , gene , physics , disease , finance , astronomy , economics
Previous studies based on serological HLA phenotyping have implicated genes in the HLA class II region in susceptibility to and protection from primary sclerosing cholangitis. In a recent report, the HLA DRw52a antigen was present in all 29 patients who had been referred for liver transplantation. In this study, HLA DRB, DQA and DQB genotypes were studied using gene amplification and sequence‐specific oligonucleotide probing in 71 patients with primary sclerosing cholangitis and 68 healthy controls to determine the frequency among the patients of the DRB3 ★ 0101 allele that encodes DRw52a and whether other class II alleles are involved in susceptibility or protection. DRB3 ★ 0101 was the most strongly associated allele, being present in 55% of the patients and 22% of the controls. Survival among the DRB3 ★ 0101‐positive patients was reduced compared with the DRB3 ★ 0101‐negative patients. Both DRB3 ★ 0101 and DRB5 ★ 0101, a possible second DRB susceptibility allele, encode a leucine residue at position 38 of the DRβ molecule. The DRB4 ★ 0101 allele, which encodes DRw53 and may be protective, encodes an alanine residue at this position. Susceptibility to and protection from primary sclerosing cholangitis may result from amino acid substitutions at position 38 of the DRβ molecule because maximum relative risk was conferred by two leucine‐38–containing DRβ molecules, whereas minimum relative risk was conferred by two alanine‐38–containing molecules. (H EPATOLOGY 1992;16:390–395.)