Frank-Bertoncelj Mojca, Klein Kerstin, Gay Steffen
Center of Experimental Rheumatology, University Hospital Zurich, Switzerland.
Epigenomics. 2017 Apr;9(4):493-504. doi: 10.2217/epi-2016-0142. Epub 2017 Mar 21.
Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors contribute to RA. High-throughput technologies for interrogating genome and epigenome, and the availability of genetic and epigenetic datasets across a diversity of cell types, enable the identification of candidate causal genetic variants for RA to study their function in core RA processes. To date, RA risk variants were studied in the immune cells but not joint resident cells, for example, synovial fibroblasts. Synovial fibroblasts from different joints are distinct, anatomically specialized cells, defined by joint-specific transcriptomes, epigenomes and phenotypes. Cell type-specific analysis of epigenetic changes, together with genetic fine mapping and interrogation of chromatin 3D interactions may identify new disease relevant pathways, potential therapeutic targets and biomarkers for RA progression or therapy response.
遗传和环境因素会增加类风湿性关节炎（RA）的发病风险，表观遗传学可能是风险因素导致RA的一个潜在关联环节。用于研究基因组和表观基因组的高通量技术，以及跨多种细胞类型的遗传和表观遗传数据集，使得识别RA的候选因果遗传变异并研究其在RA核心进程中的功能成为可能。迄今为止，RA风险变异已在免疫细胞中进行了研究，但尚未在关节驻留细胞（如滑膜成纤维细胞）中进行研究。来自不同关节的滑膜成纤维细胞是不同的、具有解剖学特异性的细胞，由关节特异性转录组、表观基因组和表型所定义。对表观遗传变化进行细胞类型特异性分析，结合遗传精细定位和染色质三维相互作用研究，可能会发现与RA相关的新疾病途径、潜在治疗靶点以及RA进展或治疗反应的生物标志物。
