血管内皮细胞生长因子受体基因启动子区多态与脑卒中复发的关系  

Association of Vascular Endothelial Growth Factor Receptor 2 Gene Promoter Variants With the Risk of Stroke Recurrence

作　　者：张伟丽[1] 祝立新[1] 孙凯[1] 王曙霞[1] 汪道文[2] 惠汝太 

机构地区：[1]中国医学科学院,北京协和医学院,心血管病研究所,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),北京市100037 [2]华中科技大学同济医学院附属同济医院,心血管内科

出　　处：《中国循环杂志》2009年第4期292-295,共4页Chinese Circulation Journal

基　　金：国家973重点基础研究发展规划基金(G2006CB503805);国家自然科学基金(30670862)

摘　　要：目的:探讨血管内皮细胞生长因子受体(VEGFR-2)基因启动子区多态与颈动脉粥样硬化以及脑卒中复发风险的关系。方法:对1849例脑卒中患者进行前瞻性随访4.5年(中位数,范围0.1～6.0年),Cox生存回归模型分析基因多态与脑卒中复发风险的关联性。并在一个横断面队列研究中随机入选1123名无心脑血管病史的参加者,检测颈动脉内膜—中膜厚度,观察基因多态与动脉粥样硬化的关系。结果:长期随访过程中,355例患者发生脑卒中复发事件。携带-604TC和CC基因型的脑卒中患者4.5年累积复发率为17.1%(159/929,复发/总例数),而-604TT基因型携带者的累积复发率为21.3%(:196/920,复发/总例数)。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,-604TC和CC基因型与降低的脑卒中复发风险相关,风险比0.71(95%可信区间,0.58～0.89;P=0.002);这种保护作用对动脉粥样硬化性血栓性脑梗塞患者更为显著,降低复发风险达35%。多元线性回归分析表明-604C等位基因与颈动脉内膜—中膜厚度呈显著负相关(标化回归系数β=0.125;P<0.001)。结论:VEGFR-2基因启动子多态-604TC和CC基因型携带者与-604TT基因型相比,脑卒中复发风险相对较低,尤其在动脉粥样硬化性血栓性脑梗塞患者中作用更显著。其机制可能与影响动脉粥样硬化的进展有关。Objective ： To assess the relationship of the variants in promoter region of vascular endothelial growth factor receptor 2 （ VEG- FR-2） gene in susceptibility to the risk of stroke recurrence. Methods ： A total of 1849 stroke patients were prospectively followed up from （ 0. 1 - 6. 0） years for a median of 4. 5 years, Cox proportional-hazards models were used to examine the association between genotypes and stroke recurrence after adjustment of age,sex,and other cardiovascular risk factors. The correlation of variants with carotid artery intima-media thickness （IMT） was examined in 1123 healthy participants as the control study. Results：There were 355 recurrent stroke patients were documented. The recurrence occurred in 17. 1% of carriers with CC and TC genotypes （ 159/929 ）, and in 21.3 % of carriers with-604 TT genotype （ 196/920 ）. The variant-604 C allele was associated with the reduced risk for stroke recurrence（ RR 0. 71,95% CI 0. 58 to 0. 89 ;P =0. 002） compared with the TT genotype,and the protective effect was stronger in patients with atherosclerotic stroke. In addition, the presence of-604 C allele was correlated w{th the lower carotid artery IMT（P 〈0. 001 ）. Conclusion：Promoter variant-604T/C in VEGFR-2 gene contributed to a redueed risk for stroke reeurrence, especially for atherosclerotie stroke. This might be through a down-regulated angiogenesis of VEGF signaling in the progress of atherosclerosis.

关 键 词：血管内皮细胞生长因子受体 遗传变异 脑卒中 复发 动脉粥样硬化 

分 类 号：R54[医药卫生—心血管疾病]