title: Association of eNOS and Cav-1 gene polymorphisms with susceptibility risk of large artery atherosclerotic stroke.
abstract: Endothelial nitric oxide synthase (eNOS) is localized in caveole and has important effects on caveolar coordination through its interaction with caveolin-1 (Cav-1), which supports normal functioning of vascular endothelial cells. However, the relationship between genotypic polymorphisms of e-NOS and Cav-1 genes and ischemic stroke (IS) remains lesser reported. This hospital-based case-control study aimed to determine the genetic polymorphisms of the eNOS (Glu298Asp) and Cav-1 (G14713A and T29107A) 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 Asp298 variant was 1.72 (95% CI = 1.09-2.75) versus Glu298 of the eNOS. In the GA/AA (rs3807987) variant, it was 1.79 (95% CI = 1.16-2.74) versus GG and in TA/AA (rs7804372) was 1.61 (95% CI = 1.06-2.43) versus TT of the Cav-1, respectively. A tendency toward an increased LAA stroke risk was significant in carriers with the eNOS Glu298Asp variant in conjunction with the G14713 A and T29107A polymorphisms of the Cav-1 (aOR = 2.03, P-trend = 0.002). A synergistic effect between eNOS and Cav-1 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 eNOS Glu298Asp and Cav-1 14713A/29107A polymorphisms are associated with the elevated risk of LAA stroke among Han Chinese in Taiwan.
authors.affiliation: Section of Neurology, Department of Internal Medicine, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.|Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hann-Yeh
authors.initials: HY
authors.lastname: Shyu
authors.affiliation: Section of Neurology, Department of Internal Medicine, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.|Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Shieh
authors.affiliation: Section of Neurology, Department of Internal Medicine, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Ling-Rong
authors.initials: LR
authors.lastname: Yen
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.|Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D051242:Caveolin 1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III