HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients.
To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4 were significantly more frequent in patients with autoimmune hepatitis than in controls. HLA-DR4 was most frequently associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher in autoimmune hepatitis than in controls. However, there was no significant difference in the frequency of Dw between the patients and the controls who were DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.
Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
T
T
Seki
M
M
Ota
S
S
Furuta
H
H
Fukushima
T
T
Kondo
K
K
Hino
N
N
Mizuki
A
A
Ando
K
K
Tsuji
H
H
Inoko
D000328:Adult; D000368:Aged; D000483:Alleles; D001327:Autoimmune Diseases / Q000208:ethnology / Q000276:immunology*; D015415:Biomarkers; D004198:Disease Susceptibility; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D015804:HLA-DR4 Antigen / Q000235:genetics; D006521:Hepatitis, Chronic / Q000208:ethnology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
D015415:Biomarkers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D015804:HLA-DR4 Antigen; D000949:Histocompatibility Antigens Class II