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Modern Rheumatology Volume 27, 2017 - Issue 3
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Original Article

Genome-wide DNA methylation patterns in CD4+ T cells from Chinese Han patients with rheumatoid arthritis

Shicheng GuoDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China,
,
Qi ZhuDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China,
,
Ting JiangDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China, ;Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China,
,
Rongsheng WangDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China, ;Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China,
,
Yi ShenDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China, ;Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China,
,
Xiao ZhuGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Dongguan Scientific Research Center, Guangdong Medical University, Dongguan, China,
,
Yan WangDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China,
,
Fengmin BaiDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China, ;Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China,
,
Qin DingDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China, ;Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China,
,
Xiaodong ZhouUniversity of Texas Medical School at Houston, Houston, TX, USA, and
,
Guangjie ChenDepartment of Immunology and Microbiology, Shanghai JiaoTong University School of Medicine, Shanghai, ChinaCorrespondence[email protected]
&
Dong Yi HeDepartment of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, Shanghai, China, ;Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China, Correspondence[email protected]
 show all
Pages 441-447 | Received 01 Feb 2016, Accepted 26 Jul 2016, Published online: 01 Sep 2016
 
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Abstract

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA.

Method: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray.

Result: The DNA methylation profiling showed 383 hyper- and 785 hypo-methylated genes in the CD4 + T cells of the RA patients (p < 3.4 × 10−7). Gene ontology analysis indicated transcript alternative splicing and protein modification mediated by DNA methylation might play an important role in the pathogenesis of RA. In addition, the result showed that human leukocyte antigen (HLA) region including HLA-DRB6, HLA-DQA1 and HLA-E was frequently hypomethylated, but HLA-DQB1 hypermethylated in CpG island region and hypomethylated in CpG shelf region in RA patients. Outside the MHC region, HDAC4, NXN, TBCD and TMEM61 were the most hypermethylated genes, while ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9 are the most hypomethylated genes.

Conclusion: Genome-wide DNA methylation profile revealed significant DNA methylation change in CD4 + T cells from patients with RA.

Acknowledgements

We thank all participating subjects for their kind cooperation in this study.

Conflict of interest

Authors declare no conflicts of interest.

This work was funded by the National Natural Science Funds of China (81273979), Shanghai clinical base construction of traditional Chinese medicine (ZY3-LCPT-1), Shanghai intensive entity construction of integrated traditional and western medicine rheumatoid arthritis (zxbz2012-05) and Shanghai clinical intensive subject construction of traditional Chinese medicine-traditional Chinese rheumatology (ZYXK2012012).

Supplementary material available online.

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