Pulse lineResearch With Heart Logo

NOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: the Atherosclerosis Risk in Communities study.

TitleNOS3 polymorphisms, cigarette smoking, and cardiovascular disease risk: the Atherosclerosis Risk in Communities study.
Publication TypeJournal Article
Year of Publication2006
AuthorsLee CR, North KE, Bray MS, Avery CL, Mosher M J, Couper DJ, Coresh J, Folsom AR, Boerwinkle E, Heiss G, Zeldin DC
JournalPharmacogenet Genomics
Volume16
Issue12
Pagination891-9
Date Published2006 Dec
ISSN1744-6872
KeywordsAfrican Americans, Alleles, Base Sequence, Cardiovascular Diseases, Cohort Studies, Coronary Disease, DNA Primers, European Continental Ancestry Group, 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
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.

DOI10.1097/01.fpc.0000236324.96056.16
Alternate JournalPharmacogenet Genomics
PubMed ID17108813
PubMed Central IDPMC1978174
Grant ListHL 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