HLA-DRB1 shared epitope-dependent DR-DQ haplotypes are associated with both anti-CCP-positive and -negative rheumatoid arthritis in Chinese Han

Xu Liu; Jianping Guo; Yuan Jia; Yi Zhao; Xia Liu; Feng Cheng; Xiaoxia Li; Yi Zheng; Xuhua Shi; Haiyun Li; Cibo Huang; Yongjing Cheng; Bei Lai; Yanhong Huang; Tian Wang; Bo Ding; Zhangguo Li

doi:10.1371/journal.pone.0071373

HLA-DRB1 shared epitope-dependent DR-DQ haplotypes are associated with both anti-CCP-positive and -negative rheumatoid arthritis in Chinese Han

PLoS One. 2013 Aug 12;8(8):e71373. doi: 10.1371/journal.pone.0071373. eCollection 2013.

Authors

Xu Liu¹, Jianping Guo, Yuan Jia, Yi Zhao, Xia Liu, Feng Cheng, Xiaoxia Li, Yi Zheng, Xuhua Shi, Haiyun Li, Cibo Huang, Yongjing Cheng, Bei Lai, Yanhong Huang, Tian Wang, Bo Ding, Zhangguo Li

Affiliation

¹ Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Amino Acid Motifs
Amino Acid Sequence
Arthritis, Rheumatoid / genetics*
Arthritis, Rheumatoid / immunology*
Asian People
Autoantibodies / immunology*
Case-Control Studies
China
Epitopes / chemistry
Epitopes / genetics*
Epitopes / immunology
Female
Genetic Association Studies
Genetic Predisposition to Disease
HLA-DQ Antigens / genetics*
HLA-DQ Antigens / immunology
HLA-DQ alpha-Chains / genetics
HLA-DQ alpha-Chains / immunology
HLA-DQ beta-Chains / genetics
HLA-DQ beta-Chains / immunology
HLA-DR Antigens / genetics*
HLA-DR Antigens / immunology
HLA-DRB1 Chains / genetics*
HLA-DRB1 Chains / immunology
Haplotypes
Humans
Male
Middle Aged
Odds Ratio
Peptides, Cyclic / immunology*

Substances

Autoantibodies
Epitopes
HLA-DQ Antigens
HLA-DQ alpha-Chains
HLA-DQ beta-Chains
HLA-DQA1 antigen
HLA-DQB1 antigen
HLA-DR Antigens
HLA-DRB1 Chains
Peptides, Cyclic
cyclic citrullinated peptide

Grants and funding

This study was financially supported by National Basic Research Program of China (973 Program) (No. 2010CB529105), General Program of the National Natural Science Foundation of China (No. 30901319), Program of International Science & Technology Cooperation from MOST (No: 2010DFB34000), Major International Joint Research Project from Natural Science Foundation of China (No: 81120108020), Doctoral Fund of Ministry of Education of China (No: 20110001110045) and Beijing Natural Science Foundation(No: 7122196). The funders of the manuscript had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.