Humanitas Clinical and Research Center-IRCCS, via Manzoni 56, 20089, Rozzano, Milan, Italy.
BIOMETRA department, University of Milan, Milan, Italy.
Adv Exp Med Biol. 2020;1253:95-104. doi: 10.1007/978-981-15-3449-2_3.
Genomic predisposition fails to fully explain the onset of complex diseases, which is well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and non-coding RNA, are the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. Autoimmune diseases now include almost 100 conditions and are estimated to cumulatively affect up to 5% of the world population with a healthcare expenditure superior to cancer worldwide. Many advances in medicine have been made to treat these conditions but there are still gaps, and an innovative and efficient therapy is needed. Systemic autoimmune diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, polymyositis, and dermatomyositis. Monozygotic twins discordant for any disease offer an ideal study design as they are matched for many factors, including genetic variation and this is a real advantage for epigenetics study. We will herein discuss the available data in the epigenetic differences leading to disease discordance in MZ twins for systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.
基因组倾向并不能完全解释复杂疾病的发生,这在同卵双胞胎之间的大部分不完全一致性中得到了很好的说明。表观遗传机制,包括 DNA 甲基化、染色质重塑和非编码 RNA,是自身免疫和慢性炎症性疾病中环境刺激与允许遗传背景下疾病发生之间的联系。自身免疫性疾病现在包括近 100 种疾病,据估计,全球有高达 5%的人口累积受到影响,其医疗支出超过全球癌症。为了治疗这些疾病,医学已经取得了许多进展,但仍存在差距,需要一种创新和有效的治疗方法。系统性自身免疫性疾病包括类风湿关节炎、系统性红斑狼疮、系统性硬皮病、干燥综合征、多发性肌炎和皮肌炎。任何疾病的同卵双胞胎不一致都提供了一个理想的研究设计,因为它们在许多因素上是匹配的,包括遗传变异,这对表观遗传学研究是一个真正的优势。我们将在此讨论在系统性红斑狼疮、类风湿关节炎和系统性硬皮病中导致 MZ 双胞胎疾病不一致的表观遗传差异的现有数据。