DNA甲基化异常与先天性心脏病的研究进展

先天性心脏病（congenital heart disease，CHD）是人类最常见的出生缺陷之一，发病率约为1%。CHD病因复杂，目前大部分病因尚不完全清楚。除了遗传因素，人们越来越多的从表观遗传学的角度探寻CHD的发病机制。DNA甲基化是目前研究最广泛的表观遗传机制，胚胎发育不同阶段DNA甲基化的失调，可导致组织特异性基因的异常沉默，从而增加心脏发生畸形的风险。不同组织中特异性CpG岛甲基化位点之间存在相关性，通过分析外周血细胞甲基化变化与心脏组织甲基化变化之间的联系可以找出一些可能的生物标志物，从而建立CHD发病的预测模型。本文就DNA甲基化在CHD，尤其是法洛氏四联症（Tetralogy of Fallot，TOF）发病中的作用机制，对DNA甲基化调控CHD发病的研究进展进行论述总结。

Research progress of abnormal DNA methylation and congenital heart disease

Congenital heart disease (CHD) is one of the most common birth defects in humans, with a incidence of about 1%. The etiology of CHD is complex, and most of the etiologies are not completely clear at present. In addition to genetic factors, more and more people are increasingly exploring the pathogenesis of CHD from the perspective of epigenetics. DNA methylation is the most widely studied epigenetic mechanism. The maladjustment of DNA methylation at different stages of embryonic development can lead to abnormal silencing of tissue-specific genes, thus increasing the risk of heart malformation. There is correlation between specific CpG island methylation sites in different tissues. By analyzing the correlation between methylation changes in peripheral blood cells and methylation changes in heart tissues, some possible biomarkers can be found to establish a prediction model for CHD incidence. This article reviews the mechanism of DNA methylation in the pathogenesis of CHD, especially Tetralogy of Fallot (TOF), and summarizes the research progress of DNA methylation in regulating the pathogenesis of CHD.