Combination of HLA-A and HLA class II alleles controls the susceptibility to rheumatoid arthritis.
Two hundred and four unrelated Japanese patients with rheumatoid arthritis (RA) were typed for HLA by serological typing and DNA typing. The serological typing revealed that frequencies of HLA-A11, DR4, DR53 and DQ4 were increased and those of DR8 and DQ1 were decreased in the patients. The DNA typing has precisely defined the disease-associated HLA class II alleles; DRBl*0405, DQAl*03 and DQBl*0401 showed positive associations, while negative associations were found with DRBl*0803, DQAl*0103 and DQBl*0601. The risk for RA was found to be closely associated with particular amino acid sequences of DR-beta chain, including glycine residue at the 86th position in addition to those between 70 and 74, which are known to confer binding specificity and affinity to antigenic peptides. The observation that the frequency of HLA-A11 was increased in the DRBl*0405-positive patients suggested the interaction of these two alleles in the susceptibility to RA. On the other hand, the frequency of DPB1*0201 was increased in the DRBl*0405-negative patients and the frequency of HLA-A2 was increased in the DPBl*0201-positive patients, especially in the younger onset group. These findings suggested that the combination of HLA-A2 and DPBl*0201 may confer the susceptibility in the DRBl*0405-negative patients. Our results suggested the possibility that the susceptibility to RA is controlled by the interaction of HLA-A and DRBl genes or by that of HLA-A and DPBl genes in different patient subgroups.
Tsuchiya
K
K
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan. tsuchiya@mocha.ocn.ne.jp
Kimura
A
A
Kondo
M
M
Nishimura
Y
Y
Sasazuki
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D015234:HLA-A Antigens; D006681:HLA-D Antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens