PT  - JOURNAL ARTICLE
AU  - Hong Zhu
AU  - Long-Fei Wu
AU  - Xing-Bo Mo
AU  - Xin Lu
AU  - Hui Tang
AU  - Xiao-Wei Zhu
AU  - Wei Xia
AU  - Yu-Fan Guo
AU  - Ming-Jun Wang
AU  - Ke-Qin Zeng
AU  - Jian Wu
AU  - Ying-Hua Qiu
AU  - Xiang Lin
AU  - Yong-Hong Zhang
AU  - Yao-Zhong Liu
AU  - Neng-Jun Yi
AU  - Fei-Yan Deng
AU  - Shu-Feng Lei
TI  - Rheumatoid arthritis–associated DNA methylation sites in peripheral blood mononuclear cells
AID  - 10.1136/annrheumdis-2018-213970
DP  - 2019 Jan 01
TA  - Annals of the Rheumatic Diseases
PG  - 36--42
VI  - 78
IP  - 1
4099  - http://ard.bmj.com/content/78/1/36.short
4100  - http://ard.bmj.com/content/78/1/36.full
SO  - Ann Rheum Dis2019 Jan 01; 78
AB  - Objectives To identify novel DNA methylation sites significant for rheumatoid arthritis (RA) and comprehensively understand their underlying pathological mechanism.Methods 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 construction; (4) validation tests of 10 differential methylation positions (DMPs) of interest and corresponding gene expressions; (5) correlation between PARP9 methylation and its mRNA expression level in Jurkat cells and T cells from patients with RA; (6) testing the pathological functions of PARP9 in Jurkat cells.Results A total of 1046 DNA methylation positions were associated with RA. The identified DMPs have regulatory effects on mRNA expressions. Causal inference tests identified six DNA methylation–mRNA–RA regulatory chains (eg, cg00959259-PARP9-RA). The identified DMPs and genes formed an interferon-inducible gene interaction network (eg, MX1, IFI44L, DTX3L and PARP9). Key DMPs and corresponding genes were validated their differences in additional samples. Methylation of PARP9 was correlated with mRNA level in Jurkat cells and T lymphocytes isolated from patients with RA. The PARP9 gene exerted significant effects on Jurkat cells (eg, cell cycle, cell proliferation, cell activation and expression of inflammatory factor IL-2).Conclusions This multistage study identified an interferon-inducible gene interaction network associated with RA and highlighted the importance of PARP9 gene in RA pathogenesis. The results enhanced our understanding of the important role of DNA methylation in pathology of RA.