Centre for Diabetes and Metabolic Medicine, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, UK.
Diabetes Metab Res Rev. 2013 Jan;29(1):8-18. doi: 10.1002/dmrr.2375.
Autoimmune diseases arise when the body mounts an immune response against 'self' cells and tissues causing inflammation and damage. It is commonly accepted that these diseases develop because of the interplay of genetic and environmental factors. Evidence for genetic factors includes the higher concordance of disease in monozygotic twins than in dizygotic twins. However, monozygotic twins may remain discordant for disease indicating a role for environmental factors. Environmental factors may alter gene expression via epigenetic mechanisms. This is particularly pertinent in type 1 diabetes in which DNA methylation and histone modifications have been associated with altered gene expression. The low disease concordance rate in adult-onset type 1 diabetes (<20%) suggests that environmental and epigenetic changes may play a predominant role. Defining the role of epigenetic changes could identify specific gene pathways and dysregulated expression of gene products that contribute to the pathogenesis of type 1 diabetes. This article reviews how epigenetic mechanisms may contribute to the development of autoimmune diseases with a focus on type 1 diabetes.
自身免疫性疾病是当身体对“自身”细胞和组织发起免疫反应，导致炎症和损伤时发生的。人们普遍认为，这些疾病的发展是由于遗传和环境因素的相互作用。遗传因素的证据包括同卵双胞胎比异卵双胞胎疾病的一致性更高。然而，同卵双胞胎也可能在疾病上存在不一致，这表明环境因素的作用。环境因素可以通过表观遗传机制改变基因表达。这在 1 型糖尿病中尤为相关，其中 DNA 甲基化和组蛋白修饰与改变的基因表达有关。成人发病的 1 型糖尿病（<20%）的低疾病一致性表明，环境和表观遗传变化可能起主要作用。确定表观遗传变化的作用可以确定特定的基因途径和基因产物的失调表达，这些都有助于 1 型糖尿病的发病机制。本文综述了表观遗传机制如何有助于自身免疫性疾病的发展，重点是 1 型糖尿病。
