title: Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dipartimento di Medicina, Chirurgia e Odontoiatria, Clinica Chirurgica Generale, Università degli Studi di Milano-Polo S. Paolo, Via A. Di Rudinì 8, I-20142 Milan, Italy. giorgio.ghilardi@unimi.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ghilardi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Biondi
authors.forename: Marco
authors.initials: M
authors.lastname: DeMonti
authors.forename: Mara
authors.initials: M
authors.lastname: Bernini
authors.forename: Olivia
authors.initials: O
authors.lastname: Turri
authors.forename: Federico
authors.initials: F
authors.lastname: Massaro
authors.forename: Emma
authors.initials: E
authors.lastname: Guagnellini
authors.forename: Roberto
authors.initials: R
authors.lastname: Scorza
mesh_terms: D000368:Aged; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000473:pathology; D003251:Constriction, Pathologic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III