La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA,
Curr Rheumatol Rep. 2013 Nov;15(11):372. doi: 10.1007/s11926-013-0372-9.
Epigenetic anomalies are emerging as key pathogenic features of rheumatoid arthritis (RA). The effect of epigenetics in RA ranges from contributing to complex disease mechanisms to identifying biomarkers for early diagnosis and response to therapy. This review focuses on three key epigenetic areas in RA, namely DNA methylation, histone modification, and expression and/or function of microRNAs. Epigenomics studies of DNA methylation have identified alterations of genome-wide DNA methylation in cells from patients with rheumatoid arthritis. Histone modification studies have focused on histone acetylation, which tends to be increased in RA. Preclinical studies show that inhibitors of histone deacetylases are effective in cellular and animal models of RA. Genome-wide and candidate microRNA surveys identified increased or reduced expression of selected microRNAs in rheumatoid arthritis. These microRNA are either pro or anti-inflammatory in multiple cell types or affect osteoclast physiology and the pathogenesis of bone erosion. Defining epigenetic contributions to the pathogenesis of RA, especially in combination with understanding genetic associations, could lead to novel therapy and a clearer understanding of disease risk.
表观遗传异常正成为类风湿关节炎 (RA) 的关键致病特征。表观遗传学在 RA 中的作用范围从有助于复杂的疾病机制到确定用于早期诊断和治疗反应的生物标志物。这篇综述重点介绍 RA 中的三个关键表观遗传领域，即 DNA 甲基化、组蛋白修饰以及 microRNA 的表达和/或功能。对 DNA 甲基化的表观基因组学研究已经确定了来自类风湿关节炎患者的细胞中全基因组 DNA 甲基化的改变。组蛋白修饰研究集中在组蛋白乙酰化上，RA 中组蛋白乙酰化往往会增加。临床前研究表明，组蛋白去乙酰化酶抑制剂在 RA 的细胞和动物模型中有效。全基因组和候选 microRNA 调查确定了类风湿关节炎中选定 microRNA 的表达增加或减少。这些 microRNA 在多种细胞类型中具有促炎或抗炎作用，或者影响破骨细胞生理学和骨侵蚀的发病机制。确定表观遗传对 RA 发病机制的贡献，尤其是与遗传关联的理解相结合，可能会导致新的治疗方法和对疾病风险的更清晰认识。
