Department of Genetics, UCL Institute of Ophthalmology, London, UK.
Immunology. 2012 Oct;137(2):131-8. doi: 10.1111/j.1365-2567.2012.03623.x.
Autoimmune disorders are a complex and varied group of diseases that are caused by breakdown of self-tolerance. The aetiology of autoimmunity is multi-factorial, with both environmental triggers and genetically determined risk factors. In recent years, it has been increasingly recognized that genetic risk factors do not act in isolation, but rather the combination of individual additive effects, gene-gene interactions and gene-environment interactions determine overall risk of autoimmunity. The importance of gene-gene interactions, or epistasis, has been recently brought into focus, with research demonstrating that many autoimmune diseases, including rheumatic arthritis, autoimmune glomerulonephritis, systemic lupus erythematosus and multiple sclerosis, are influenced by epistatic interactions. This review sets out to examine the basic mechanisms of epistasis, how epistasis influences the immune system and the role of epistasis in two major autoimmune conditions, systemic lupus erythematosus and multiple sclerosis.
自身免疫性疾病是一组复杂多样的疾病,由自身耐受的破坏引起。自身免疫的病因是多因素的,既有环境触发因素,也有遗传决定的危险因素。近年来,人们越来越认识到遗传危险因素并非孤立作用,而是个体加性效应、基因-基因相互作用和基因-环境相互作用的组合决定了自身免疫的总体风险。基因-基因相互作用(或上位性)的重要性最近受到了关注,研究表明,许多自身免疫性疾病,包括风湿性关节炎、自身免疫性肾小球肾炎、系统性红斑狼疮和多发性硬化症,都受到上位性相互作用的影响。这篇综述旨在探讨上位性的基本机制,上位性如何影响免疫系统,以及上位性在两种主要自身免疫疾病,即系统性红斑狼疮和多发性硬化症中的作用。