Bellvitge Biomedical Research Institute, Barcelona, Spain.
Nat Rev Rheumatol. 2011 May;7(5):263-71. doi: 10.1038/nrrheum.2011.16. Epub 2011 Feb 22.
The potential roles of epigenetic alterations in the pathogenesis of autoimmune rheumatic diseases are raising great expectations among clinicians and researchers. Epigenetic mechanisms regulate gene expression and are sensitive to external stimuli, bridging the gap between environmental and genetic factors. Considerable evidence of epigenetic changes, particularly altered patterns of DNA methylation, exists in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. The importance of such changes in the pathology of rheumatic diseases has been demonstrated by examining the relationship between gene-specific methylation and SLE in monozygotic twins discordant for the disease, in whom genetic variability is excluded as a cause for discordance. Several studies have highlighted the importance of the tissue-specificity of DNA methylation changes, an aspect which-in contrast with genetic analysis-must be considered when designing epigenetic studies. Here I discuss the proposed mechanisms and implications of DNA methylation changes in the pathogenesis of autoimmune rheumatic diseases, the prospects for future epigenetic studies in rheumatology, the relevance of specific DNA methylation markers and the potential use of drugs with an epigenetic effect in the clinical management of these diseases.
表观遗传改变在自身免疫性风湿性疾病发病机制中的潜在作用，在临床医生和研究人员中引发了巨大的期望。表观遗传机制调节基因表达，对外界刺激敏感，在环境和遗传因素之间架起了桥梁。在系统性红斑狼疮 (SLE) 和类风湿关节炎等疾病中，存在大量的表观遗传改变证据，特别是 DNA 甲基化模式的改变。通过检查疾病不一致的同卵双胞胎中基因特异性甲基化与 SLE 之间的关系，证明了这种变化在风湿性疾病病理学中的重要性，因为在这种情况下，遗传变异性不能作为不一致的原因。几项研究强调了 DNA 甲基化变化的组织特异性的重要性，与遗传分析相比，在设计表观遗传研究时必须考虑到这一点。在这里，我讨论了 DNA 甲基化变化在自身免疫性风湿性疾病发病机制中的提出的机制和意义、风湿病学中未来表观遗传研究的前景、特定 DNA 甲基化标志物的相关性以及在这些疾病的临床管理中使用具有表观遗传效应的药物的潜力。
