Dataset Information

Rheumatoid arthritis associated DNA methylation sites in peripheral blood mononuclear cells

ABSTRACT: Genome wide DNA methylation profiling of rheumatoid arthritis (RA) patients and healthy controls. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles in peripheral blood mononuclear cells (PBMCs). Samples included 25 RA patients and 18 healthy controls. Overall design: To identify more rheumatoid arthritis (RA) associated DNA methylation sites and comprehensively understand their underlying pathologic mechanism, we compared the Illumina Infinium 450k Human DNA methylation microarray data from PBMCs of 25 RA patients with that of 18 healthy controls.

INSTRUMENT(S): Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)

SUBMITTER: Xingbo Mo

PROVIDER: GSE111942 | GEO | 2018-10-14

REPOSITORIES: GEO

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Publications

Rheumatoid arthritis-associated DNA methylation sites in peripheral blood mononuclear cells.

Zhu Hong H Wu Long-Fei LF Mo Xing-Bo XB Lu Xin X Tang Hui H Zhu Xiao-Wei XW Xia Wei W Guo Yu-Fan YF Wang Ming-Jun MJ Zeng Ke-Qin KQ Wu Jian J Qiu Ying-Hua YH Lin Xiang X Zhang Yong-Hong YH Liu Yao-Zhong YZ Yi Neng-Jun NJ Deng Fei-Yan FY Lei Shu-Feng SF

Annals of the rheumatic diseases 20181008 1

<h4>Objectives</h4>To identify novel DNA methylation sites significant for rheumatoid arthritis (RA) and comprehensively understand their underlying pathological mechanism.<h4>Methods</h4>We performed (1) genome-wide DNA methylation and mRNA expression profiling in peripheral blood mononuclear cells from RA patients and health controls; (2) correlation analysis and causal inference tests for DNA methylation and mRNA expression data; (3) differential methylation genes regulatory network construct ...[more]

PMID: 30297333

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Project description:Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints involved with genetic and epigenetic aberrant. Recent evidence found more and more importance of the epigenetic contribution, especially the DNA methylation, to the pathogenesis of rheumatoid arthritis. To understand the extent and nature of dysregulated DNA methylation in rheumatoid arthritis T cells, we performed a genome-wide DNA methylation study in CD4+ T cells in 12 rheumatoid arthritis patients compared to 12 matched normal healthy controls. [Methods and Result] Cytosine methylation status was quantified with Illumina methylation 450K microarray (HM450K, 485512 CpG sites). We identified 810 hypomethylated and 392 hypermethylated CG sites in RA CD4+ T cells compared to normal controls, representing 383 and 785 genes hypermethylated and hypomethylated in RA patients (P<3.4*10-7). Cluster analysis based on significantly differential methylated loci showed distinct separation between RA and normal controls. Gene ontology analysis showed alternative splicing (P=1.2*10-7, FDR) and phosphoprotein (1.7*10-2, FDR) were significantly aberrant in RA patients, indicating the abnormal of transcript alternative splicing and protein modification mediated by DNA methylation might play important role in the pathogenesis of rheumatoid arthritis. What’s more, the result showed human leukocyte antigen (HLA) region was frequently hypomethylated in RA patients, including HLA-DRB6, HLA-DQA1 and HLA-E, however, HLA-DQB1 showed different methylation profiles with significant hypermethylation in CpG island region and hypomethylation in CpG shelf region. Outsite of the MHC region, the most hypermethylated genes in RA included HDAC4, NXN, TBCD and TMEM61 while the most significant hypomethylated genes included ITIH3, TCN2, PRDM16, SLC1A5 and GALNT9. [Conclusion] Genome-wide DNA methylation patterns revealed significant DNA methylation change in CD4+ T cells from patients with rheumatoid arthritis. 12 rheumatoid arthritis and 12 matched health individuals Overall design: Bisulphite converted DNA from the CD4+ T cell extracted from Rheumatoid arthritis 12 patients and age, gender, race matched 12 normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays