Luan Meiwei, Shang Zhenwei, Teng Yanbo, Chen Xinren, Zhang Mingming, Lv Hongchao, Zhang Ruijie
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Oncotarget. 2017 Jul 19;8(65):108355-108374. doi: 10.18632/oncotarget.19383. eCollection 2017 Dec 12.
Interaction between genetic and epigenetic mechanisms may lead to autoimmune diseases. The features of these diseases show familial aggregation. The generality and specificity are keys to studying pathogenesis and etiology of them. This research integrated data of genetics and epigenetics, to find disease-related genes based on the levels of expression and regulation, and explored then to the shared and specific mechanism of them by analyzing shared and specific pathways of common four autoimmune diseases, including Type 1 Diabetes Mellitus (T1D), Multiple Sclerosis (MS), Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). The results showed that Lysosome and Fc gamma R-mediated phagocytosis are shared pathways of the four diseases. It means that the occurrence and development of them may associate with lysosomes and phagocytosis. And there were 2 pathways are shared pathways of three diseases ribosome pathway associated with susceptibility to MS, RA and SLE, and Pathogenic infection associated with susceptibility to T1D, MS and RA; 9 pathways are shared pathways of two diseases. The corporate underlying causes of these diseases may be these shared pathways activated. Furthermore, we found that T1D-related specific pathways (Insulin signaling,etc.) were 9, MS (Proteasome,etc.) is also 9, RA and SLE is 10 and 6 respectively. These pathways could help us to reveal shared and specific mechanisms of the four diseases.
遗传机制与表观遗传机制之间的相互作用可能导致自身免疫性疾病。这些疾病的特征表现出家族聚集性。普遍性和特异性是研究其发病机制和病因的关键。本研究整合了遗传学和表观遗传学数据，基于表达和调控水平寻找疾病相关基因，并通过分析1型糖尿病（T1D）、多发性硬化症（MS）、类风湿性关节炎（RA）和系统性红斑狼疮（SLE）这四种常见自身免疫性疾病的共同和特定途径，探索它们的共同和特定机制。结果表明，溶酶体和FcγR介导的吞噬作用是这四种疾病的共同途径。这意味着它们的发生和发展可能与溶酶体和吞噬作用有关。有2条途径是三种疾病的共同途径，核糖体途径与MS、RA和SLE的易感性相关，致病性感染与T1D、MS和RA的易感性相关；9条途径是两种疾病的共同途径。这些疾病的共同潜在病因可能是这些共同途径被激活。此外，我们发现与T1D相关的特定途径（胰岛素信号传导等）有9条，MS（蛋白酶体等）也有9条，RA和SLE分别有10条和6条。这些途径有助于我们揭示这四种疾病的共同和特定机制。
