Association of Genetic Polymorphisms on Vascular Endothelial Growth Factor and its Receptor Genes with Susceptibility to Coronary Heart Disease

Abstract

BackgroundCoronary heart disease (CHD) is a cardiovascular disease characterized by high morbidity and mortality. Vascular endothelial growth factor (VEGF) and its receptor, named kinase insert domain-containing receptor (KDR, or VEGFR2), which are involved with angiogenesis and vascular repair, could partly contribute to the development of CHD. The aim of this study, therefore, was to investigate the potential correlations between genetic polymorphisms on VEGF and KDR and susceptibility to CHD, and the integrative role of SNPs combined on susceptibility to CHD were also studied.Material/MethodsVenous blood samples gathered from 533 DCM patients and 533 healthy controls were used to genotype tag-SNPs of VEGF (rs699947, rs2010963, and rs3025010) and KDR (rs2071559, rs2305948, and rs1870377) by polymerase chain reaction (PCR) and SNaPshot assay. Investigations of potential haplotypes were conducted on the basis of SHEsis software. The odds ratio (ORs) and relevant 95% confidence intervals (95% CI) were used to estimate associations of SNPs/haplotypes with risk of CHD. Multivariate logistic regression was also performed, taking certain clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension) into consideration. All statistical analyses were done with STATA Version 12.0 software.ResultsOur results suggest that rs699947 (T>C) on KDR are associated with susceptibility to CHD under the dominant model before (OR=1.35, 95% CI: 1.05–1.73, P=0.019) and after (OR=1.33, 95% CI: 1.01–1.76, P=0.044), allowing for clinical characteristics (e.g., BMI, smoking, alcohol consumption, diabetes, and hypertension). rs2305948 (G>A) and rs1870377 (A>T) on VEGF were also found to be associated with risk of CHD under the recessive model after adjustment with multivariate regression analyses (OR=1.21, 95% CI: 1.02–1.43, P=0.029; OR=2.54, 95% CI: 1.13–5.75, P=0.025); OR=2.83, 95% CI: 1.47–5.46, P=0.002, respectively). Additionally, haplotype analyses revealed that integration of 5 SNPs would either raise (e.g. C-C-T-G-T and T-G-T-G-T) or reduce (e.g. C-C-C-G-T, T-C-T-G-A, T-C-T-G-T, and T-G-T-G-A) risk of CHD.ConclusionsGenetic polymorphisms on VEGF (rs699947) and KDR (rs2305948and rs1870377), as well as relevant haplotypes, may serve as genetic markers that might be useful in future investigations on the pathogenesis of CHD.

Single‐nucleotide polymorphisms of VEGF‐A and VEGFR‐2 genes and risk of infantile hemangioma

“…As far as we know, this study is the first to analyze the association of polymorphisms in VEGFR‐2 gene with IH. Nevertheless, there are some literature data suggesting the linkage between examined VEGFR‐2 polymorphisms and such diseases like, for example, coronary heart disease, glioma, or sarcoidosis . In our analysis of genotype frequencies, we have showed a lack of significant differences in distribution of genetic variants between cases and controls for both examined VEGFR‐2 polymorphisms.…”

“…Regarding this, we have investigated the role of two functional polymorphisms of gene coding for VEGF receptor‐2: +1416 T/A and −271 G/A. A mutant allele of +1416 T/A polymorphism has been found to reduce the affinity of VEGF for its receptor 2 and A/A genotype of −271 G/A polymorphism has been shown to correlate with lower VEGFR‐2 protein levels . In the result, this may dysregulate the VEGF/VEGFR‐2 signaling pathway.…”

“…37 However, Jinnin et al 14 T/A polymorphism has been found to reduce the affinity of VEGF for its receptor 2 39 and A/A genotype of À271 G/A polymorphism has been shown to correlate with lower VEGFR-2 protein levels. 40 In the result, this may dysregulate the VEGF/ VEGFR-2 signaling pathway.…”

Association between VEGF Gene Polymorphisms and In-Stent Restenosis after Coronary Intervention Treated with Bare Metal Stent

“…Merlo et al found significant association between VEGF levels and rs2010963 polymorphism but observed no association with carotid intima-media thickness [40]. Moreover, in a recent study [23] this SNP was not found to be associated with coronary artery disease. We found a significant association of rs2010963 VEGF polymorphism and the development of diffuse in-stent restenosis in our study population.…”

Regional Aspects of the Gene Polymorphism Vеgfr2 With Coronary Atherosclerosis in Acute Coronary Syndrome

“…1 Известно, что эндотелиальная дисфункция при коронарном атеросклерозе ассоциирована с поли-морфизмом ряда генов, определяющих функцию эндотелия [1,2]. В последние годы активно изучается влияние аллельных вариантов гена рецептора II типа фактора роста эндотелия сосудов (VEGFR2), регули-рующего функцию эндотелия, на течение коронар-ной болезни сердца [3]. Ввиду того, что в российских регионах и в частности в Сибири отмечаются суще-ственные различия в этнической структуре населения [4] целью настоящего исследования явилась оценка ассоциаций аллельного варианта гена VEGFR2 rs2305948 с атеросклеротическим поражением коро-нарных артерий (КА) у пациентов с острым коронар-ным синдромом (ОКС) на Севере (Сургут) и в круп-ных городах Сибирского федерального округа России (Новосибирск, Иркутск и Кемерово).…”