Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity
Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity
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DOI：
10.1007/s12016-015-8502-y
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发表时间：
2016-06
影响因子：
9.1
通讯作者：
Yu-Qing Xie;Hong-Di Ma;Zhe‐Xiong Lian
中科院分区：
文献类型：
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作者：
Yu-Qing Xie;Hong-Di Ma;Zhe‐Xiong Lian
原发性胆汁性肝硬化（PBC）是一种基于遗传和环境因素相互作用而发展的慢性炎症性自身免疫性疾病。最近的全基因组关联研究（GWAS）已经确定了数十种易感变异，包括hla、IL12A和ctla4，但在确定“确凿证据”方面却令人失望。这些发现强调了遗传背景在免疫失调中的重要性。尽管在自身免疫性疾病中，单卵双胞胎PBC的一致性率是最高的，但已证实与差异表达基因相关的双胞胎存在不完全疾病一致性。然而，对于环境因素是如何导致这种疾病的，以及为什么中年妇女更容易患这种疾病，人们知之甚少。因此，表观遗传因子将指示环境变化的信号转化为转录潜能的动态和可遗传的改变，在基础和临床研究中越来越受到研究人员的关注。在表观遗传机制中，X染色体的不稳定性和基因表达偏斜可能解释了PBC中女性的优势。此外，组蛋白修饰和DNA甲基化的转录调控强调了疾病发病机制的潜在参与。高通量技术被用于识别表观遗传调控因子。在这篇综述中，我们试图概述关于PBC和其他自身免疫性疾病的表观遗传学的最新进展。
Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified dozens of predisposing variants includingHLA,IL12A, andCTLA4but have been disappointed in identifying a “smoking gun.” These discoveries highlight the importance of the genetic background involved in immunological dysregulation. Although concordance rate of PBC in monozygotic (MZ) twins is among the highest reported in autoimmune disorders, incomplete disease concordance in twins associated with differentially expressed genes has been demonstrated. However, little is understood about how environmental aspects contribute to the disease and why middle-aged women are more susceptible. As a result, epigenetic factors, which convert signals indicating environmental changes into dynamic and heritable alterations of transcriptional potential, are getting increased attention by researchers in both basic and clinical studies. Among epigenetic mechanisms, the instability and skewed gene expression in the X chromosome may account for the female preponderance in PBC. In addition, transcriptional regulation of histone modification and DNA methylation underscores potential involvement in disease pathogenesis. High-throughput techniques are being used to identify epigenetic regulators. In this review, we attempt to outline recent progress regarding epigenetics in PBC and other autoimmune diseases.