Polymorphisms of KDR gene are associated with coronary heart disease
Polymorphisms of KDR gene are associated with coronary heart disease
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DOI：
10.1016/j.jacc.2007.04.074
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发表时间：
2007-08-21
影响因子：
24
通讯作者：
Hui, Rutal
中科院分区：
文献类型：
--
作者：
Wang, Yibo;Zheng, Yi;Hui, Rutal
目的本研究的目的是确定是否有常见的多态性，血管内皮生长因子（Vascular endothelial growth factor，VEGF）及其受体KDR（receptor KDR，KDR）基因多态性（SNP-604，SNP 1192，SNP 1719）与冠心病的发病风险相关。（含激酶插入结构域的受体/胎肝激酶-1，也称为VEGFR 2）在血管生成和血管修复中起关键作用，方法在2个独立的病例对照研究中确定3个多态性与冠心病风险的关联：一组包括665名冠心病患者和1,015名对照组，另一组包括369名患者和625名对照组。结果2项独立人群研究均显示KDR基因的3个多态性与冠心病的危险性相关，SNP-604的OR值为1.37（p = 0.006），SNP 1192为1.41（p = 0.011），SNP 1719为1.37在第一群体中，SNP-604为1.40（p = 0.015），SNP 1192为1.75（p = 0.003），SNP 1719为1.50（p = 0.010）。携带SNP-604 C的KDR启动子表现出比携带SNP-604 T的启动子低68%的转录活性。SNP 1192和SNP 1719可显著影响VEGF与KDR的结合效率。结论KDR基因多态性可作为冠心病危险性的新的遗传标记。
Objectives Our purpose was to determine whether the common polymorphisms (SNP-604, SNP1192, and SNP1719) in KDR are associated with risk of coronary heart disease.Background Vascular endothelial growth factor (VEGF) and its receptor KDR (kinase insert domain-containing receptor/fetal liver kinase-1, also called VEGFR2) play critical roles in angiogenesis and vascular repair, which are involved in the progress of coronary heart disease.Methods The association of the 3 polymorphisms with risk of coronary heart disease was determined in 2 independent case-control studies: one comprised of 665 patients with coronary heart disease and 1,015 control subjects, and the other comprised of 369 patients and 625 control subjects. The SNP functions of KDR gene were studied by using luciferase reporter assays, determination of serum levels of KDR, and ligand-binding assays.Results The 2 independent population studies showed that the 3 polymorphisms were associated with risk of coronary heart disease with odds ratios of 1.37 for SNP-604 (p = 0.006), 1.41 for SNP1192 (p = 0.011), and 1.37 for SNP1719 (p = 0.007) in the first population, and 1.40 for SNP-604 (p = 0.015), 1.75 for SNP1192 (p = 0.003), and 1.50 for SNP1719 (p = 0.010) in the second population. The SNP-604C-bearing KDR promoter exhibited 68% of lower transcription activity than the SNP-604T-bearing promoter. The SNP1192 and SNP1719 could obviously influence the efficiency of VEGF binding to KDR.Conclusions The KDR polymorphisms may serve as novel genetic markers for the risk of coronary heart disease.