Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke

<div><p>Endothelial nitric oxide synthase (<i>eNOS</i>) is localized in caveole and has important effects on caveolar coordination through its interaction with caveolin-1 (<i>Cav-1</i>), which supports normal functioning of vascular endothelial cells. However, the relationship between genotypic polymorphisms of <i>e-NOS</i> and <i>Cav-1</i> genes and ischemic stroke (IS) remains lesser reported. This hospital-based case-control study aimed to determine the genetic polymorphisms of the <i>eNOS</i> (<i>Glu298Asp</i>) and <i>Cav-1</i> (<i>G14713A</i> and <i>T29107A</i>) genes in association with susceptibility risk in patients who had suffered from a large artery atherosclerotic (LAA) stroke. Genotyping determination for these variant alleles was performed using the TaqMan assay. The distributions of observed allelic and genotypic frequencies for the polymorphisms were in Hardy-Weinberg equilibrium in healthy controls. The risk for an LAA stroke in the <i>Asp298</i> variant was 1.72 (95% CI = 1.09–2.75) versus <i>Glu298</i> of the <i>eNOS</i>. In the <i>GA/AA</i> (rs3807987) variant, it was 1.79 (95% CI = 1.16–2.74) versus <i>GG</i> and in <i>TA/AA</i> (rs7804372) was 1.61 (95% CI = 1.06–2.43) versus <i>TT</i> of the <i>Cav-1</i>, respectively. A tendency toward an increased LAA stroke risk was significant in carriers with the <i>eNOS Glu298Asp</i> variant in conjunction with the <i>G14713 A</i> and <i>T29107A</i> polymorphisms of the <i>Cav-1</i> (aOR = 2.03, P-_trend = 0.002). A synergistic effect between <i>eNOS</i> and <i>Cav-1</i> polymorphisms on IS risk elevation was significantly influenced by alcohol drinking, heavy cigarette smoking (P-_trend<0.01), and hypercholesterolemia (P-_trend < 0.001). In conclusion, genotypic polymorphisms of the <i>eNOS Glu298Asp</i> and <i>Cav-1 14713A/29107A</i> polymorphisms are associated with the elevated risk of LAA stroke among Han Chinese in Taiwan.</p>