Title | NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: the Atherosclerosis Risk in Communities study. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Lee CR, North KE, Bray MS, Avery CL, Mosher M J, Couper DJ, Coresh J, Folsom AR, Boerwinkle E, Heiss G, Zeldin DC |
Journal | Pharmacogenet Genomics |
Volume | 16 |
Issue | 12 |
Pagination | 891-9 |
Date Published | 2006 Dec |
ISSN | 1744-6872 |
Keywords | Alleles, Base Sequence, Black or African American, Cardiovascular Diseases, Cohort Studies, Coronary Disease, DNA Primers, Female, Genotype, Haplotypes, Humans, Longitudinal Studies, Male, Middle Aged, Nitric Oxide Synthase Type III, Polymorphism, Single Nucleotide, Proportional Hazards Models, Risk Factors, Smoking, Stroke, United States, White People |
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 >or=20 pack-year smokers carrying the variant C-786 allele relative to 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. |
DOI | 10.1097/01.fpc.0000236324.96056.16 |
Alternate Journal | Pharmacogenet Genomics |
PubMed ID | 17108813 |
PubMed Central ID | PMC1978174 |
Grant List | HL 074377 / HL / NHLBI NIH HHS / United States ES012856 / ES / NIEHS NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States Z01 ES025034-13 / / Intramural NIH HHS / United States F32 ES012856-03 / ES / NIEHS NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States F32 ES012856-01 / ES / NIEHS NIH HHS / United States F32 ES012856 / ES / NIEHS NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States F32 ES012856-02 / ES / NIEHS NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States HL073366 / HL / NHLBI NIH HHS / United States R01 HL074377 / HL / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01 HL073366 / HL / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01HC55020 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States |