Influence of HLA-DRB1 genes and the shared epitope on genetic susceptibility to rheumatoid arthritis in Taiwanese.
OBJECTIVE
To investigate the association of predisposing and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in a Taiwanese population.


METHODS
A total of 273 patients with RA and 480 healthy controls, all of Taiwanese origin, were genotyped for HLA-DRB1 alleles by polymerase chain reaction and sequence-based typing assays. The associations between RA and HLA-DRB1 alleles and genotypes were investigated by chi-squared test.


RESULTS
The DRB1*0405 and *1001 phenotypes showed the most significant associations with RA (OR 4.04, 95% CI 2.84-5.77, pc = 3.2 10(-14); OR 5.25, 95% CI 2.10-13.06, pc = 3.0 10(-3), respectively). Individuals carrying single or double doses of the shared epitope (SE/non-SE or SE/SE) had higher risks of RA. The compound heterozygote of DRB1*0405/*1001 showed the largest increase in RA risk (OR 15.8, 95% CI 2.48-100.7, pc = 0.004). Single or double doses of SE alleles were significantly associated with a higher bone erosion rate. Rheumatoid factor positivity and bone erosion were more frequent in patients with at least one copy of DRB1*0405.


CONCLUSIONS
Our results show that SE-encoding HLA-DRB1*0405 and *1001 are associated with RA in a Taiwanese population; this is the first time DRB1*1001 has been described in persons of Asian ethnicity. Heterozygotes of DRB1*0405 and *1001 predicted the strongest susceptibility to RA, suggesting that this genotype enhances susceptibility to RA in Taiwanese.
Liu
Shih-Chia
SC
Department of Orthopedic Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
Chang
Tzu-Yang
TY
Lee
Yann-Jinn
YJ
Chu
Chen-Chung
CC
Lin
Marie
M
Chen
Zong-Xian
ZX
Liu
Hsin-Fu
HF
Dang
Ching-Wen
CW
Chang
Shih-Chuan
SC
Lee
Chyou-Shen
CS
Chen
Tien-Ling
TL
Huang
Chun-Hsiung
CH
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D013624:Taiwan / Q000453:epidemiology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains