Polymorphisms of KDRGene Are Associated With Coronary Heart Disease

ObjectivesOur purpose was to determine whether the common polymorphisms (SNP-604, SNP1192, and SNP1719) in KDRare associated with risk of coronary heart disease.BackgroundVascular 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.MethodsThe 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 KDRgene were studied by using luciferase reporter assays, determination of serum levels of KDR, and ligand-binding assays.ResultsThe 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 KDRpromoter 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.ConclusionsThe KDRpolymorphisms may serve as novel genetic markers for the risk of coronary heart disease.