HLA-DRB1 shared epitope-dependent DR-DQ haplotypes are associated with both anti-CCP-positive and -negative rheumatoid arthritis in Chinese Han.
The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10(-6)). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10(-13)). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10(-13)) and -negative RA (P = 3.89×10(-5)). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
Xu
X
Liu
Jianping
J
Guo
Yuan
Y
Jia
Yi
Y
Zhao
Xia
X
Liu
Feng
F
Cheng
Xiaoxia
X
Li
Yi
Y
Zheng
Xuhua
X
Shi
Haiyun
H
Li
Cibo
C
Huang
Yongjing
Y
Cheng
Bei
B
Lai
Yanhong
Y
Huang
Tian
T
Wang
Bo
B
Ding
Zhangguo
Z
Li
D000328:Adult; D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D044466:Asian People; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D002681:China; D000939:Epitopes / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010456:Peptides, Cyclic / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide