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CLINICAL RESEARCH

Polymorphisms of KDR Gene Are Associated With Coronary Heart Disease

Yibo Wang, PhD^_*, Yi Zheng, MD^_*, Weili Zhang, PhD^_*, Hui Yu, MS^_*, Kejia Lou^_*, Yu Zhang^_*, Qin Qin, MD, Bingrang Zhao, MD, Ying Yang, MD and Rutai Hui, MD, PhD^_*,_*

^_* Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education, China and Sino-German Laboratory for Molecular Medicine, and the Department of Cardiology, Cardiovascular Institute and FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Tianjin Cardiovascular Institute and Tianjin Chest Hospital, Tianjin, China
Qingdao FuWai Hospital, Shandong, China

Manuscript received December 5, 2006; revised manuscript received April 19, 2007, accepted April 24, 2007.

^_* Reprint requests and correspondence: Dr. Rutai Hui, Cardiovascular Institute and FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishilu, Beijing 100037, People's Republic of China (Email: huirutai{at}sglab.org).

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.

Abbreviations and Acronyms   BMI = body mass index   CHD = coronary heart disease   DM = diabetes mellitus   EPC = endothelial progenitor cell   HDL-C = high-density lipoprotein cholesterol   KDR = kinase insert domain-containing receptor   PCR = polymerase chain reaction   TC = total plasma cholesterol   TG = triglycerides   SNP = single nucleotide polymorphism   VEGF = vascular endothelial growth factor

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