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

Autor: Gisela Gaspar, José M. Ferro, Tiago Krug, Sofia A. Oliveira, Isabel Albergaria, Helena Manso, Astrid M. Vicente, João Sobral
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
Pathology
Nitric Oxide Synthase Type I
Bioinformatics
Linkage Disequilibrium
Brain Ischemia
Doenças Cardio e Cérebro-vasculares
chemistry.chemical_compound
Gene Frequency
Risk Factors
Enos
Odds Ratio
Medicine
Stroke
biology
Middle Aged
Nitric oxide synthase
Phenotype
Female
Cardiology and Cardiovascular Medicine
Adult
medicine.medical_specialty
Nitric Oxide Synthase Type III
NOS1
Single-nucleotide polymorphism
Endothelial NOS
Polymorphism
Single Nucleotide
Risk Assessment
Nitric oxide
Genetics
Humans
Genetic Predisposition to Disease
cardiovascular diseases
Aged
Chi-Square Distribution
Portugal
business.industry
Haplotype
biology.organism_classification
medicine.disease
Logistic Models
Haplotypes
chemistry
Susceptibility
Case-Control Studies
Multivariate Analysis
biology.protein
business
Popis: 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 q uncorrected P q 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.
Databáze: OpenAIRE
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