Variants within the nitric oxide synthase 1 gene are associated with stroke susceptibility

• Published in: Atherosclerosis Vol. 220; no. 2; pp. 443 - 448
• Main Authors: Manso, Helena, Krug, Tiago, Sobral, João, Albergaria, Isabel, Gaspar, Gisela, Ferro, José M, Oliveira, Sofia A, Vicente, Astrid M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01-02-2012; Elsevier
• Subjects: Adult; Aged; animals; atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; blood flow; Brain Ischemia - enzymology; Brain Ischemia - genetics; Cardiology. Vascular system; Cardiovascular; Case-Control Studies; Chi-Square Distribution; endothelial nitric oxide synthase; Female; Gene Frequency; genes; Genetic Predisposition to Disease; Genetics; Haplotypes; Humans; hypertension; lifestyle; Linkage Disequilibrium; Logistic Models; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neurology; neuronal nitric oxide synthase; Nitric oxide; Nitric Oxide Synthase Type I - genetics; Nitric Oxide Synthase Type III - genetics; Odds Ratio; patients; Phenotype; Polymorphism, Single Nucleotide; Portugal; risk; Risk Assessment; Risk Factors; single nucleotide polymorphism; Stroke; Stroke - enzymology; Stroke - genetics; Susceptibility; Vascular diseases and vascular malformations of the nervous system; Portugal; Genetics; Stroke; Susceptibility; Nitric oxide; Nervous system diseases; Enzyme; Cardiovascular disease; Nitric-oxide synthase; Cerebral disorder; Vascular disease; Central nervous system disease; Atherosclerosis; Oxidoreductases; Cerebrovascular disease
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2011.11.011

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. Conclusion 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.