title: Promoter polymorphisms in the nitric oxide synthase 3 gene are associated with ischemic stroke susceptibility in young black women.
abstract: OBJECTIVE
  Endothelial nitric oxide exerts a variety of protective effects on endothelial cells and blood vessels, and therefore the nitric oxide synthase 3 gene (NOS3) is a logical candidate gene for stroke susceptibility.
  
  
  METHODS
  We used the population-based Stroke Prevention in Young Women case-control study to assess the association of five NOS3 polymorphisms in 110 cases (46% black) with ischemic stroke and 206 controls (38% black), 15 to 44 years of age. Polymorphisms included 3 single nucleotide polymorphisms (SNPs) in the promoter region (-1468 T>A, -922 G>A, -786 T>C), 1 SNP in exon 7 (G894T), and 1 insertion/deletion polymorphism within intron 4.
  
  
  RESULTS
  Significant associations with both the -922 G>A and -786 T>C SNPs with ischemic stroke were observed in the black, but not the white, population. This association was attributable to an increased prevalence of the -922 A allele (OR=3.0, 95% CI=1.3 to 6.8; P=0.005) and the -786 T allele (OR=2.9, 95% CI=1.3 to 6.4; P=0.005) in cases versus controls. These 2 SNPs were in strong linkage disequilibrium (D'=1.0), making it impossible to determine, within the confines of this genetic study, whether 1 or both of these polymorphisms are functionally related to NOS3 expression. Two sets of haplotypes were also identified, 1 of which may confer an increased susceptibility to stroke in blacks, whereas the other appears to be protective.
  
  
  CONCLUSIONS
  Promoter variants in NOS3 may be associated with ischemic stroke susceptibility among young black women.
authors.affiliation: The Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Howard
authors.forename: Wayne H
authors.initials: WH
authors.lastname: Giles
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Wozniak
authors.forename: Ann M
authors.initials: AM
authors.lastname: Malarcher
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Richard F
authors.initials: RF
authors.lastname: Macko
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Basehore
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: John W
authors.initials: JW
authors.lastname: Cole
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Kittner
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044383:Black People; D002545:Brain Ischemia / Q000208:ethnology* / Q000235:genetics*; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D020521:Stroke / Q000208:ethnology* / Q000235:genetics*; D044465:White People
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III