项目名称: 动脉粥样硬化相关的基因甲基化与缺血性脑卒中关系的家系研究
项目编号: No.81502874
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 秦雪英
作者单位: 北京大学
项目金额: 18万元
中文摘要: 缺血性脑卒中是影响我国居民健康和生活质量的公共卫生问题。缺血性脑卒中病因复杂,除遗传因素和环境因素外,表观遗传学也在缺血性脑卒中的发病中起重要作用。近年来,表观遗传学,特别是DNA甲基化修饰日益成为缺血性脑卒中病因学研究的热点,但DNA甲基化在缺血性脑卒中发病中的作用和地位仍不十分清楚。本研究针对缺血性脑卒中的致病通路之一--动脉粥样硬化,采用家系设计,在已建立的中国北方缺血性脑卒中家系人群中检测外周血总DNA甲基化状态和特定的动脉粥样硬化相关基因(雌激素受体基因、内皮型一氧化氮合酶基因、载脂蛋白E基因)的甲基化状态,运用家系资料的分析方法分析DNA甲基化与缺血性脑卒中常见危险因素、生物标志物(同型半胱氨酸、C反应蛋白、载脂蛋白E、颈动脉粥样硬化指标等)及缺血性脑卒中亚型的关系和交互作用,探讨甲基化在缺血性脑卒中发病中的可能机制,为缺血性脑卒中的预防、早期诊断和治疗提供新的依据。
中文关键词: DNA甲基化;动脉粥样硬化;缺血性脑卒中;家系研究
英文摘要: Ischemic stroke has long been a public health problem which has important influences on the population quality and health in China. The etiology of ischemic stroke is complicated, besides genetic and environmental determinants, epigenetic mechanisms may play an important role in ischemic stroke. Epigenetics, especially DNA methylation, is becoming widely concerned in the etiology of ischemic stroke in recent years, however, the exact mechanisms of DNA methylation are not completely understood. In this study, we focus on atherosclerosis, one of the critical pathogenic pathways, use a family-based design to study the relationship between DNA methylation and ischemic stroke. We examine global DNA methylation and DNA methylation on specific atherosclerosis related genes (estrogen receptor gene, endothelial nitric oxide synthase gene, and apolipoprotein E gene) with blood samples in ischemic stroke families which we recruited in previous studies, and analyze the relationship and interaction between DNA methylation and commonrisk factors, biomarkers (homocysteine, C-reactionprotein, apolipoprotein E, index of carotid atherosclerosis) and subtypes of ischemic stroke, using family-based study analyzing methods. We explore the possible underlying mechanism of DNA methylation on ischemic stroke, and expect to provide new scientific evidence for the prevention, early diagnosis and treatment of ischemic stroke.
英文关键词: DNA methylation;atherosclerosis ;ischemic stroke;family-based study