Working Paper Review Version 2 This version is not peer-reviewed

Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis

Version 1 : Received: 14 April 2020 / Approved: 15 April 2020 / Online: 15 April 2020 (09:51:14 CEST)
Version 2 : Received: 18 August 2020 / Approved: 18 August 2020 / Online: 18 August 2020 (16:16:27 CEST)

How to cite: Guo, S.; Xu, L.; Chang, C.; Zhang, R.; Jin, Y.; He, D. Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis. Preprints 2020, 2020040237 Guo, S.; Xu, L.; Chang, C.; Zhang, R.; Jin, Y.; He, D. Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis. Preprints 2020, 2020040237

Abstract

Rheumatoid arthritis (RA) is a complex disease triggered by the interaction between genetics and environment, especially through the shared epitope (SE) and cell surface calreticulin (CSC) theory. However, the available evidence shows that genetic diversity and environmental exposure cannot explain all the clinical characteristics and heterogeneity of RA. In contrast, recent studies demonstrate that epigenetics play important roles in the pathogenesis of RA, especially DNA methylation and histone modification. DNA methylation and histone methylation are involved in innate and adaptive immune cell differentiation, and migration, proliferation, apoptosis, and mesenchymal characteristics of fibroblast-like synoviocytes (FLS). Epigenetic-mediated regulation of immune-related genes and inflammation pathways explains the dynamic expression network of RA. In this review, we summarized the comprehensive evidence to show that methylation of DNA and histones is significantly involved in the pathogenesis of RA and could be applied as a promising biomarker in the disease progression and drug response prediction. We also explained the advantages and challenges of the current epigenetics research in RA. In summary, epigenetic modules provide a possible interface, through which genetic and environmental risk factors connect to contribute to the susceptibility and pathogenesis of RA. Additionally, epigenetic regulators provide promising drug targets to develop novel therapeutic drugs for RA. Finally, DNA methylation and histone modifications could be important features for providing a better RA subtype identification, to accelerate personalized treatment and precision medicine.

Keywords

Epigenetic; Methylation; Rheumatoid Arthritis; Pathogenesis; Regulation

Subject

Medicine and Pharmacology, Medicine and Pharmacology

Comments (1)

Comment 1
Received: 18 August 2020
Commenter: Lingxia Xu
Commenter's Conflict of Interests: Author
Comment: We polish the language and modify the artical according to the opinions of Frontier in Genetics.
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