Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene

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Abstract

Background: NO synthesized from L-arginine by the constitutive endothelial NO synthase (eNOS) plays a key role in the atherosclerotic process. We investigated whether common variants in the NOS3 gene (a T786C mutation in the 5′ flanking region and the polymorphism on exon 7 that produced the Glu298Arg polymorphism in the protein) are associated with an increased risk of moderate to severe internal carotid artery (ICA) stenosis. Methods: We studied 88 patients consecutively operated for ICA stenosis and 133 healthy controls. A T786C mutation in the 5′ flanking region and the polymorphism in exon 7 that produces the Glu298Asp polymorphism in the protein were explored by PCR and fluorescent probe analysis. Results: Genotype distribution was significantly different between patients and controls only for T786C, the CC genotype frequency being 26% and 13%, respectively [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.14-4.46; P = 0.018]. Moreover, the CC genotype was significantly more frequent in a subgroup of patients with ulcerative plaques compared with patients with nonulcerative lesions (44% vs 17%; OR, 3.82; 95% CI, 1.79-8.14; P = 0.003). Multiple logistic regression analysis using the most frequent risk factors and the eNOS gene variant showed that the CC genotype is an independent risk factor for ICA stenosis (P = 0.023). Conclusion: C allele homozygosity in position 786 of the eNOS promoter seems to be an independent risk factor for the development of moderate to severe ICA stenosis, especially ulcerative lesions. © 2002 American Association for Clinical Chemistry.

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Ghilardi, G., Biondi, M. L., DeMonti, M., Bernini, M., Turri, O., Massaro, F., … Scorza, R. (2002). Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene. Clinical Chemistry, 48(7), 989–993. https://doi.org/10.1093/clinchem/48.7.989

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