Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis.
OBJECTIVE
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 DRB1*0301 (corrected probability [Pc] = 0.00003; relative risk [RR] = 4.58), and a secondary association with DRB1*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*0301 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.
Strettell
M D
MD
Institute of Liver Studies, King's College Hospital and School of Medicine, London, England.
Donaldson
P T
PT
Thomson
L J
LJ
Santrach
P J
PJ
Moore
S B
SB
Czaja
A J
AJ
Williams
R
R
D000328:Adult; D000368:Aged; D000483:Alleles; D000596:Amino Acids / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000378:metabolism*; D006505:Hepatitis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged
D000596:Amino Acids; D006680:HLA Antigens