PATHOGENESIS OF RHEUMATOID ARTHRITIS: THE INTERSECTION OF GENETICS AND EPIGENETICS.
PATHOGENESIS OF RHEUMATOID ARTHRITIS: THE INTERSECTION OF GENETICS AND EPIGENETICS.
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发表时间：
2018
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通讯作者：
G. Firestein
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作者：
G. Firestein
风湿性关节炎是一种滑膜炎性疾病，其特征是免疫细胞浸润关节并破坏细胞外基质。虽然遗传学在遗传性及其发病机制中起着关键作用，但同卵双胞胎中疾病一致性的相对缺乏表明非编码影响可以影响风险和严重程度。环境压力可以在基因组中反映为改变的表观遗传标记，也有助于基因调控并有助于疾病机制。DNA甲基化的研究表明，滑膜细胞，最显着的成纤维细胞样滑膜细胞，在类风湿性关节炎与表观遗传标记的印记，并随后承担侵略性表型。更有趣的是，滑膜细胞标记不仅是疾病特异性的，而且可以根据起源的关节而变化。使用无偏方法了解表观遗传景观可以潜在地识别负责滑膜炎症的非明显途径和基因以及对靶向药物的反应多样性。这些信息也可以用来确定新的治疗方法。
Rheumatoid arthritis is a synovial inflammatory disease marked by joint infiltration by immune cells and damage to the extracellular matrix. Although genetics plays a critical role in heritability and its pathogenesis, the relative lack of disease concordance in identical twins suggests that noncoding influences can affect risk and severity. Environmental stress, which can be reflected in the genome as altered epigenetic marks, also contributes to gene regulation and contributes to disease mechanisms. Studies on DNA methylation suggest that synovial cells, most notably fibroblast-like synoviocytes, are imprinted in rheumatoid arthritis with epigenetic marks and subsequently assume an aggressive phenotype. Even more interesting, the synoviocyte marks are not only disease specific but can vary depending on the joint of origin. Understanding the epigenetic landscape using unbiased methods can potentially identify nonobvious pathways and genes that that are responsible for synovial inflammation as well as the diversity of responses to targeted agents. The information can also be leveraged to identify novel therapeutic approaches.