title: Variants within the nitric oxide synthase 1 gene are associated with stroke susceptibility.
abstract: OBJECTIVE
  Animal studies have allowed important insights into the role of the nitric oxide synthase (NOS) enzymes in atherosclerosis and hypertension, as well as in stroke. In this study we tested the hypothesis that the NOS1 and NOS3 genes, respectively encoding neuronal NOS (nNOS) and endothelial NOS (eNOS), influence stroke susceptibility and outcome after a stroke event.
  
  
  METHODS
  We conducted a case-control association study in 551 ischemic stroke patients and 530 controls to assess the role of NOS1 and NOS3 variants in stroke susceptibility. The same genes were tested for association with stroke outcome in a subset of 431 patients.
  
  
  RESULTS
  Four NOS1 single nucleotide polymorphisms (SNPs) (rs2293050, rs2139733, rs7308402 and rs1483757) and four haplotypes were significantly associated with stroke susceptibility after adjusting for demographic, clinical and life-style risk factors, and correcting for multiple testing using the false discovery rate (FDR) method (SNPs: 0.004<(uncorrected)P<0.007 and 0.036<FDR q<0.048; haplotypes: 0.001<(uncorrected)P<0.010 and 0.018<FDR q<0.032). NOS1 variants were not associated with stroke outcome. We did not find any evidence for a role of the NOS3 gene in stroke susceptibility or outcome.
  
  
  CONCLUSIONS
  Our results highlight NOS1 as a susceptibility factor for stroke, but do not corroborate previous NOS3 association findings with stroke risk. nNOS is known to play a major role in atherosclerosis development and in blood flow regulation, and it is plausible that its influence in stroke may be mediated through these two main clinical risk factors.
authors.affiliation: Departamento Promoção da Saúde e Doenças Crónicas, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisbon, Portugal. hmanso@igc.gulbenkian.pt
authors.forename: Helena
authors.initials: H
authors.lastname: Manso
authors.forename: Tiago
authors.initials: T
authors.lastname: Krug
authors.forename: João
authors.initials: J
authors.lastname: Sobral
authors.forename: Isabel
authors.initials: I
authors.lastname: Albergaria
authors.forename: Gisela
authors.initials: G
authors.lastname: Gaspar
authors.forename: José M
authors.initials: JM
authors.lastname: Ferro
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Vicente
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000235:genetics*
chemical_list: C496320:NOS1 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III