Genetic variants of vascular endothelial growth factor gene polymorphism affect the risk and severity of ischemic stroke: a case–control study

Abstract

<br><b>Background and objectives</b><br>Vascular endothelial growth factor (VEGF) is the key mediator of angiogenesis and atherosclerosis. Hence, it may play a major role in the pathogenic mechanisms underlying ischemic stroke (IS) progression. Thus, we conducted this case–control study to explore the genetic association of a single gene polymorphism of VEGF + 936C/T (rs3025039) with the risk and severity of IS and its relation with serum VEGF level.<br><b>Patients and methods</b><br>This study included a case series of 49 patients with IS with 41 controls. VEGF + 936C/T (rs3025039) variants were determined via Taqman allelic discrimination PCR. Serum VEGF level was estimated using enzyme-linked immunosorbent assay. The frequency of VEGF rs3025039 genotypes and alleles was calculated manually in both cases and controls. The risk ratio was estimated and represented by odds ratio (OR) and 95% confidence interval (CI) adjusted to the confounding variables via multinomial logistic regressions. The stroke severity was assessed by National Institute of Health Stroke Scale. Moreover, serum VEGF levels were compared between the studied groups and among different genotypes and alleles of IS cases.<br><b>Results</b><br>Our study detected significantly increased frequencies of TT genotype (<i>P</i> = 0.030) and T allele (<i>P</i> = 0.045) in IS cases when compared with the controls. TT genotype represents an increased adjusted risk for IS progression by 9.94 folds (OR: 9.938, 95% CI: 1.235–79.97) and T allele by 2.19 folds (OR: 2.191, 95% CI: 1.004–4.782) over the CC genotypes and C allele, respectively. Moreover, TT genotypes are associated with higher National Institute of Health Stroke Scale. The serum VEGF level was significantly lower in IS cases than controls, and a more decreased level was associated with the T allele carriers in IS cases groups.<br><b>Conclusions</b><br>VEGF rs3025039 gene polymorphism is associated with increased risk and severity of IS and decreased VEGF expression, which may play a major role in the pathogenesis of IS progression.<br>