title: Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage.
abstract: OBJECTIVE
  The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3).
  
  
  METHODS
  Three hundred thirty-three Caucasian SAH patients and 498 controls were genotyped for the -922A > G (rs 1800779), -786T > C (rs2070744), and 894G > T (rs1799983) single nucleotide polymorphisms and the intron-4 27-bp variable number of tandem repeats polymorphism (27-bp-VNTR).
  
  
  RESULTS
  The b/b (5 repeats) genotype of the 27-bp-VNTR was overrepresented in cases (77%) versus controls (69%) (p = 0.02). In male patients the b/b genotype was found in 85% compared with 67% in male controls, whereas in women, the frequencies were 73% and 72%, respectively. This corresponds to an odds ratio of 2.8 (95% CI 1.5-5.6, p = 0.0005) for SAH in men with the b/b genotype versus men with a/b or a/a. In women, no such association was found (OR 1.1, 95% CI 0.7-1.6, p = 0.76). Stepwise logistic regression including arterial hypertension, smoking, sex, and age with interactions yielded similar effect estimates of the 27-bp-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect.
  
  
  CONCLUSIONS
  The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH. This effect is not mediated by any single NOS3 haplotype.
authors: Department of Neuroscience and Pharmacology, University of Copenhagen; and.
authors: Jonatan Myrup
authors: JM
authors: Staalsø
authors: Troels
authors: T
authors: Edsen
authors: Alexandros
authors: A
authors: Kotinis
authors: Bertil
authors: B
authors: Romner
authors: Jacob Bertram
authors: JB
authors: Springborg
authors: Niels Vidiendal
authors: NV
authors: Olsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012737:Sex Factors; D013345:Subarachnoid Hemorrhage / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics*; D055815:Young Adult
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: NO = nitric oxide; NOS = NO synthase; NOS3; PCR = polymerase chain reaction; SAH = subarachnoid hemorrhage; SNP = single nucleotide polymorphism; VNTR = variable number of tandem repeats; aneurysmal subarachnoid hemorrhage; nitric oxide synthase; polymorphism; vascular disorders