The HLA-DRB1 Shared Epitope (SE)-associated DR-DQ Haplotypes is Predominantly Associated with Both Anti-Cyclic Citrullinated Peptides (CCPs) antibodies-Positive and -Negative Rheumatoid Arthritis in Han Population

Liu Xu; Jianping Guo; Yuan Jia; Yi Zhao; Xia Liu; Xiaolan Lu; Feng Cheng; Xiaoxia Li; Yi Zheng; Cibo Huang; Yongjing Cheng; Tian Wang; Zhanguo Li

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The HLA-DRB1 Shared Epitope (SE)-associated DR-DQ Haplotypes is Predominantly Associated with Both Anti-Cyclic Citrullinated Peptides (CCPs) antibodies-Positive and -Negative Rheumatoid Arthritis in Han Population

Liu Xu 1,Jianping Guo 2,Yuan Jia 2,Yi Zhao 3,Xia Liu 4,Xiaolan Lu 2,Feng Cheng 5,Xiaoxia Li 3,Yi Zheng 6,Cibo Huang 7,Yongjing Cheng 7,Tian Wang 8,Zhanguo Li 2 *

1.Department of Rheumatology and Immunology, Peking University People\'s Hospital, Beijing 100044

2.Department of Rheumatology and Immunology, Peking University People's Hospital

3.Department of Rheumatology, Xuanwu Hospital Capital Medical University

4.Department of Rheumatology, China-Japan Friendship Hospital

5.Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences

6.Department of Rheumatology, Chao-yang Hospital

7.Department of Rheumatology, Beijing Hospital of the Ministry of Health

8.Department of Internal Medicine, Beijing Anzhen Hospital Capital Medical University

*Correspondence author

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Funding: Doctoral Fund of Ministry of Education of China（No.No: 20090001110082 and No: 20110001110045）, National Basic Research Program of China (973 Program)（No.No. 2010CB529105）, General Program of the National Natural Science Foundation of China（No.No. 30901319）, Program of International Science & Technology Cooperation from MOST （No.No: 2010DFB34000）, Major International Joint Research Project from NSFC（No.No: 81120108020）, Beijing Natural Science Foundation（No.No: 7122196）

Opened online:23 January 2013

Accepted by: none

Citation: Liu Xu ,Jianping Guo,Yuan Jia.The HLA-DRB1 Shared Epitope (SE)-associated DR-DQ Haplotypes is Predominantly Associated with Both Anti-Cyclic Citrullinated Peptides (CCPs) antibodies-Positive and -Negative Rheumatoid Arthritis in Han Population[OL]. [23 January 2013] http://en.paper.edu.cn/en_releasepaper/content/4515774

Introduction: The association between Human Leukocyte Antigen (HLA) class II alleles and rheumatoid arthritis (RA) has been extensively studied in multiple ethnic groups, but few have been reported in Chinese Han population. In this work, we investigated the association of HLA-DRB1, DQA1, DQB1, and the DRB1- DQA1-DQB1 (DR-DQ) haplotypes with RA susceptibility and with RA-specific antibodies against cyclic citrullinated peptides (anti-CCP) in Han population. Methods: High-resolution HLA-DRB1, DQA1 and DQB1 genotyping were performed in 281 RA patients and 202 healthy controls. The associations between DRB1, DQA1 and DQB1 alleles or haplotypes and RA susceptibility were evaluated. The presence of anti-CCP antibodies was analyzed in carriers of the different DR-DQ haplotypes. Results: The HLA-DRB1 shared epitope (SE)-encoding alleles *0101, *0405 and *0410 were highly susceptible to RA in Han population. In which, *0405 displayed the most significant RA association (P=3.65×10-6). The grouped SE alleles showed great association with RA susceptibility (P=4.37 x 10-10). The DRB1 D70 alleles displayed significant protective effects against RA (P=1.00 x 10-3). The haplotype DQA1*03-DQB1*0401(DQ4) displayed increased susceptibility to RA (P=1.60 x 10-3). In terms of DR-DQ haplotypes, the SE-DQ3/4/5 haplotypes remained strong association with RA susceptibility independent of DQ status (P=1.93 x 10-8), whereas the DRB1 D70-associated DR-DQ haplotypes conferred a strong protective effect against RA (P=9.20 x 10-4). Furthermore, the presence of SE-DQ3/4/5 haplotype was strongly associated with both anti-CCP positive (P=4.50 x 10-9) and anti-CCP negative RA (P=4.56 x 10-3). Conclusions: Our study revealed that the HLA-DRB1 SE alleles and its haplotypes SE-DQ3/DQ4/DQ5 were highly associated with RA susceptibility in Han population. The DRB1 D70 alleles and its haplotypes D70-DQ3 /DQ5 displayed strong protective effects against RA. The HLA DR-DQ haplotypes containing RA susceptible or protective alleles were mainly associated with anti-CCP positive RA. However, the SE-DQ3/DQ4/DQ5 haplotypes were also associated with anti-CCP negative RA.

Keywords:Rheumatoid arthritis; human leukocyte antigen (HLA); shared epitope; DR-DQ haplotypes; anti-CCP

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