血管内皮细胞生长因子受体基因编码区变异与脑卒中复发及心血管病死率的研究  

Variant Val297Ile in the VEGFR-2 gene contributes to the risk of stroke recurrence and cardiovascular mortality in a large prospective stroke population

作　　者：张伟丽[1] 孙凯[1] 祝立新[1] 陈宇[1] 廖玉华[2] 万鲁红 秦勤[4] 汪道文[5] 马爱群[6] 祝之明 惠汝太 

机构地区：[1]中国医学科学院中国协和医科大学阜外心血管病医院心血管病相关基因与临床研究教育部重点实验室(中德分子医学研究室),北京100037 [2]华中科技大学协和医院心内科华中科技大学同济医学院心血管病研究所 [3]兖州矿业(集团)三十七处医院 [4]天津市胸科医院天津市心血管病研究所 [5]华中科技大学同济医学院附属同济医院心内科 [6]西安交通大学第一医院急诊科 [7]重庆市大坪高血压病研究所

出　　处：《临床心血管病杂志》2009年第6期421-425,共5页Journal of Clinical Cardiology

基　　金：国家973重点基础研究发展规划的资助项目(No:G2006CB503805);国家自然科学基金资助项目(No:30670862)

摘　　要：目的:血管发育异常、损伤修复能力下降等将影响血管的正常结构与功能,与心脑血管疾病的发生及预后密切相关。本文探讨血管内皮细胞生长因子受体(VEGFR-2)基因编码区变异Val297Ile对脑卒中复发风险及心血管病死率的影响。方法:自2000-2001年在全国7个临床中心入选1849例脑卒中患者(35～74岁),进行前瞻性随访4.5年(中位数,范围0.1～6.0年),收集脑卒中复发和死亡事件。Cox生存回归模型分析基因变异与脑卒中复发及病死率的关系。结果:长期随访过程中,355例发生脑卒中复发事件,180例死于心血管病事件。携带297Ile等位基因的脑卒中患者4.5年累积复发率为24.3%,心血管病死率为13.6%,显著高于297Val携带者(分别为17.4%和8.4%)。Cox生存回归模型校正了年龄、性别和其他心血管危险因素后,297Ile等位基因与增加的脑卒中复发风险(RR:1.40,95%CI1.12～1.75;P=0.003)和心血管病死率(RR:1.64,95%CI1.21～2.23;P=0.002)相关。结论:VEGFR-2基因编码区变异297Ile是一个与脑卒中高复发风险和心血管病死率相关的新的预测因子,其机制与受损血管内皮的修复能力下降有关。Objective： Dysfunctions of vessel wall formation and endothelial integrity play critical roles in atherogenesis and stroke. We tested whether variant Va1297Ile in the gene encoding vascular endothelial growth factor receptor-2 （VEFGR-2） contributes to the risk of stroke recurrence and cardiovascular mortality in a large prospective stroke population. Method：A total of 1 849 patients with stroke （35 74 years） were recruited in the Multicenter Chinese Stroke Study during 2000 2001 and prospectively followed up for a median of 4. 5 years （range, 0.1-6.0 years）. Cox proportional-hazards model was used to analysis the association between genotypes and stroke recurrence or long term mortality. Result：During the longterm follow up, 355 recurrent strokes and 180 deaths （180 from cardiovascular diseases and 143 from other causes） were documented. The cumulative incidences of stroke recurrence and cardiovascular mortality were significantly higher in the carriers with 297Ile allele （24.3and 13.6%, respectively） than in those with the wild-type 297Val/Val （17.4% and 8.4%, respectively）. After adjustment for age, gender, and other cardiovascular risk factors, variant 297Ile was significantly associated with increased risk of stroke recurrence and long-term cardiovascular mortality compared with the 297Val/Val geno- type; relative risks （RRs） were 1.40 （95% CI： 1.12-1.75） for stroke recurrence （P=0. 003） and 1.64 （95% CI： 1.21-2.23） for cardiovascular mortality （P=0. 002）. Conclusion： Our findings suggest that VEGFR-2 gene variant 297Ile may serve as a novel genetic predictor for the high risk of stroke recurrence and long-term cardiovascular mortality.

关 键 词：脑卒中 血管内皮细胞生长因子受体 遗传变异 复发 

分 类 号：R743.3[医药卫生—神经病学与精神病学]