Association of Genetic Polymorphisms on VEGFA and oronary He se VEGFR 2 With Risk of C

Coronary heart disease (CHD) is a cardiovascular disease which is contributed by abnormal neovascularization. VEGFA (vascular endothelial growth factor A) andVEGFR2 (vascular endothelial growth factor receptor 2) have been revealed to be involved in the pathological angiogenesis. This study was intended to confirm whether single nucleotide polymorphisms (SNPs) of VEGFA andVEGFR2 were associated with CHD in a Chinese population, considering pathological features and living habits of CHD patients. Peripheral blood samples were collected from 810 CHD patients and 805 healthy individuals. Six tag SNPs within VEGFA andVEGFR2 were obtained from HapMap Database. Genotyping of SNPs was performed using SNapShot method (Applied Biosystems, Foster, CA). Odd ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated to evaluate the association between SNPs and CHD risk. Under the allelic model, 6 SNPs of VEGFA and VEGFR2 were remarkably associated with the susceptibility to CHD. Genotype CT of rs3025039, TT of rs2305948, and AA of rs1873077 were associated with a reduced risk of CHD when smoking, alcohol intake and diabetes were considered, while homozygote GG of rs1570360 might elevate the susceptibility to CHD (all P< 0.05) for patients who were addicted to smoking or those with hypertension. All of the combined effects of rs699947 (CC/CA) and rs2305948 (TT), rs3025039 (TT) and rs2305948 (TT), rs3025039 (CT) and rs1870377 (AA) had positive effects on the risk of CHD, respectively (all P< 0.05). By contrast, the synthetic effects of rs69947 (CA/AA) and rs1870377 (TA), rs699947 (CA) and rs7667298 (GG), rs699947 (AA) and rs7667298 (GG), rs1570360 (GG) and rs2305948 (TT), as well as rs1570360 (GG) and rs1870377 (AA) all exhibited adverse effects on the risk of CHD, respectively (all P< 0.05). Six polymorphisms in VEGFA and VEGFR2 may have substantial influence on the susceptibility to CHD in a Han Chinese population. Prospective cohort studies should be further designed to confirm the above conclusions. Zunqi Liu, MD, Mulin Cong, MD, and Bo Hu, MD allele frequency, OR = odd ratio, SNP = single nucleotide polymorphism, VEGFA = vascular endothelial growth factor A, VEGFR2 = vascular endothelial growth factor receptor 2. INTRODUCTION C oronary heart disease (CHD) is a cardiovascular disease with high morbidity and mortality, contributing to a total of 379,559 deaths in America in 2010. Moreover, about 75% deaths resulted from CHD occurred in underdeveloped and developing countries. The development of CHD could be attributed to genetic predisposition and nongenetic risk factors, including smoking status, alcohol consumption, stress, diabetes, and lack of exercise. The interaction between genetic and nongenetic risk factors may have significant impact on the development of CHD and many single nucleotide polymorphisms (SNPs) that are associated with CHD have been identified by genome-wide association studies (GWAS). Angiogenesis dysfunction was hitherto considered as a contributor to CHD since it is related with an elevated susceptibility to atherosclerosis, hypertension and diabetes, which are the three crucial CHD-causing maladies. Accordingly, mutations of maladies-related SNPs within certain genes would probably render subjects more vulnerable to CHD, such as rs10491334 in CaMK4, PI (A1/A2) polymorphisms in glycoprotein IIIa and so on. It has been suggested that both vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor 2 (VEGFR2) were involved in neovascularization, vasopermeability regulation, and formation of blood vessel networks. The 2 heredity genes also seemed to alter the risk of hypertension among targeted populations. VEGFA is located on chromosome 6 and it could express different isoforms of proteins. The VEGF family contains VEGF-A,VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, and placental growth factor (PIGF), in which VEGF-A is often referred as VEGF. Several SNPs of VEGF-A identified by single-stranded conformational polymorphism analysis and sequencing have been linked with the development of coronary artery disease, endometriosis, peripheral artery disorder, and lung cancer. Furthermore, mutations of VEGFR2 SNPs (e.g., rs2071559) have also been demonstrated to be related with numerous diseases including tumors, rheumatoid arthritis, proliferative retinopathies, and CHD. However, there are few studies which are able to clarify the intrinsic relationship between VEGFA/VEGFR2 genetic polymorphisms and the susceptibility to CHD. Bioinformatics enabled us to discover that rs7667298 is located in the promoter region of VEGFR2 and exonic polymorphisms of rs2305948 and rs1870377 are both situated in the of VEGFR2. Meanwhile, both rs699947 ated in the promoter region of VEGFA, een suggested to be associated with the www.md-journal.com | 1 development of CHD by formal studies. Therefore, the association between 6 VEGFA/VEGFR2 genetic polymorphisms and the risk of CHD in a Chinese Han population was clarified by our study which also adjusted for several confounding factors including smoking status, alcohol consumption, hypertension and diabetes. The additive effects of the SNPs on the susceptibility to CHD were also evaluated in the 810 CHD cases and 805 healthy controls, providing us with applicable strategies for treatment of CHD. MATERIALS AND METHODS