Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis

被引:225
作者
Strettell, MDJ
Donaldson, PT
Thomson, LJ
Santrach, PJ
Moore, SB
Czaja, AJ
Williams, R
机构
[1] UNIV LONDON KINGS COLL HOSP, INST LIVER STUDIES, LONDON SE5 9PJ, ENGLAND
[2] UNIV LONDON SCH MED, LONDON, ENGLAND
[3] MAYO CLIN & MAYO FDN, DIV TRANSFUS MED, ROCHESTER, MN 55905 USA
[4] MAYO CLIN & MAYO FDN, DIV GASTROENTEROL & INTERNAL MED, ROCHESTER, MN 55905 USA
[5] UCL, SCH MED, INST HEPATOL, LONDON W1N 8AA, ENGLAND
关键词
D O I
10.1053/gast.1997.v112.pm9178696
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: In a recent study, we suggested that susceptibility to type 1 autoimmune hepatitis is associated with a six-amino acid motif, LLEQKR, within the DR beta polypeptide, but these data are in conflict with contemporary reports from Japan and Argentina. The purpose of the present study was to reexamine this question in a large independent cohort of patients, Methods: Eighty-six North American white patients and 102 control subjects were studied, HLA class I antigens were determined serologically, and the DRB1, DQA1, DQB1, and DPB1 genes and the DRB3/ 4/5 subtypes were determined by high-resolution genotyping. Results: The greatest risk was associated with DPB1*0301 (corrected probability [Pc] = 0.00003; relative risk [RR] = 4.58), and a secondary association with DPB1*0401 was identified (Pc = 0.000132; RR = 5.97), Protection from disease was associated with the DRB5*0101-DRB1*1501 haplotype (Pc = 0.021; RR = 0.3), However, further analysis indicated that a lysine residue at position 71 of the DR beta polypeptide may be the most important determinant of disease susceptibility (P = 0.0000003; RR = 8.6, increasing to RR = 16.38 with four lysine residues). Conclusions: DRB1*0302 and DRB1*0401 are confirmed as the principal susceptibility alleles for type 1 autoimmune hepatitis, and these data support the hypothesis that a lysine residue at position 71 of the DR beta-polypeptide chain may be the major risk factor.
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页码:2028 / 2035
页数:8
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