基因多态性作为缺血性脑卒中预后生物标志物的研究

项目名称： 基因多态性作为缺血性脑卒中预后生物标志物的研究

项目编号： No.81200914

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 刘改芬

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 近年来，全基因组关联研究与候选基因研究发现了某些基因多态性如位于12p13、4q25和9p21的SNPs，以及MTHFR，PED4D和TNF-α等与缺血性卒中发病呈关联关系。然而这些基因多态性作为急性缺血性脑卒中预后的影响的研究还鲜有报道。本研究以临床确诊、国际公认的缺血性卒中SSS-TOAST分型的首发、急性缺血性脑卒中为研究对象，采用前瞻性队列研究方法，研究上述基因多态性与急性缺血性脑卒中病后残疾、心血管事件、脑卒中再发和死亡的关联关系及关联强度，从中筛选出对缺血性脑卒中预后预示作用强的标志物；探讨这些基因多态性与传统危险因素对缺血性脑卒中病后残疾、心血管事件、脑卒中再发和死亡的交互效应。本研究将为基因多态性与缺血性脑卒中预后的关系提供重要的流行病学证据，也将为缺血性脑卒中病后二级预防策略提供新思路。

中文关键词： 缺血性卒中；基因多态性；预后；联合终点事件；相关性

英文摘要： Recently, genome wide association study and candidate gene study found some genetic polymorphisms on 12p13, 4q25 and 9p21,and MTHFR, PED4D and TNF-αet. al. were significantly associated with ischemic stroke. However, there is rare studies on the association between these genetic ploymorphisms and the outcome of ischemic stroke. This study aims to detect the association between above genetic polymorphisms and the outcome of ischemic stroke in first-ever, acute ischemic stroke patiens with clincal and SSS-TOAST subtype diagnosis, in a prospective study.The outcome indices includes disability, cardiovascular events, recurrence of stroke and death. Base on the association study, single nucleotide polymorphisms (SNPs)which strongly associated with the outcome will be selected as biomarkers of ischemic stroke outcome. Interactions of genetic polymorphisms with traditinal risk factor such as age, gender, medical history will also be detected. This large scale study aims to provide important epidemiological evidence for the asscoiation between genetic polymorphism and ischemic stroke outcome, and furthermore, new insight into the personalized secondary preventive stratigies.

英文关键词： ischemic stroke；genetic polymorphism；unfavorable outcome；combined endpoint event；association