NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study. [Pharmacogenet Genomics] Journal article | | Title | NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: The Atherosclerosis Risk in Communities study. | | Author(s) | Lee CR, North KE, Bray MS, Avery CL, Mosher MJ, Couper DJ, Coresh J, Folsom AR, Boerwinkle E, Heiss G, Zeldin DC | | Institution | aDivision of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park bDivision of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy Departments of cEpidemiology dBiostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina eChildrenʼs Nutrition Research Center, Baylor College of Medicine fThe Human Genetics Center, University of Texas Health Science Center, Houston, Texas gDepartment of Epidemiology, The Johns Hopkins University, Baltimore, Maryland hDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA. | | Source | Pharmacogenet Genomics 2006 Dec; 16(12):891-899. | | Abstract | OBJECTIVE: Endothelial nitric oxide synthase (NOS3) activity and cigarette smoking significantly influence endothelial function. We sought to determine whether cigarette smoking modified the association between NOS3 polymorphisms and risk of coronary heart disease or stroke.
METHODS: All 1085 incident coronary heart disease cases, all 300 incident ischemic stroke cases, and 1065 reference individuals from the Atherosclerosis Risk in Communities study were genotyped for the T-786C and E298D polymorphisms in NOS3. Using a case-cohort design, associations between genotype/haplotype and disease risk were evaluated by multivariable proportional hazards regression. Multiplicative scale interaction testing evaluated the influence of cigarette smoking history at baseline on these associations.
RESULTS: In Caucasians, association between E298D genotype and risk of coronary heart disease was significantly modified by current smoking status (interaction P=0.013), with the highest risk observed in smokers carrying the variant D298 allele relative to nonsmokers carrying two E298 alleles (adjusted hazard rate ratio 2.07, 95% confidence interval 1.39-3.07). In African-Americans, association between T-786C genotype and risk of ischemic stroke was significantly modified by pack-year smoking history (interaction P=0.037), with the highest risk observed in >/=20 pack-year smokers carrying the variant C-786 allele relative to <20 pack-year smokers carrying two T-786 alleles (adjusted hazard rate ratio 4.03, 95% confidence interval 1.54-10.6).
CONCLUSIONS: An interaction between the E298D and T-786C polymorphisms in NOS3, cigarette smoking, and risk of incident coronary heart disease and ischemic stroke events appears to exist, suggesting a potential complex interplay between genetic and environmental factors and cardiovascular disease risk. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17108813 |
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