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Cyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study.

TitleCyclooxygenase polymorphisms and risk of cardiovascular events: the Atherosclerosis Risk in Communities (ARIC) study.
Publication TypeJournal Article
Year of Publication2008
AuthorsLee CR, North KE, Bray MS, Couper DJ, Heiss G, Zeldin DC
JournalClin Pharmacol Ther
Volume83
Issue1
Pagination52-60
Date Published2008 Jan
ISSN1532-6535
KeywordsAfrican Americans, Aspirin, Atherosclerosis, Biomarkers, Case-Control Studies, Coronary Disease, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase Inhibitors, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Longitudinal Studies, Male, Middle Aged, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Stroke, Thromboxane B2, United States
Abstract

Cyclooxygenase-derived prostaglandins modulate cardiovascular disease risk. We genotyped 2212 Atherosclerosis Risk in Communities study participants (1,023 incident coronary heart disease (CHD) cases; 270 incident ischemic stroke cases; 919 non-cases) with available DNA for polymorphisms in PTGS1 and PTGS2. Using a case-cohort design, associations between genotype and CHD or stroke risk were evaluated using proportional hazards regression. In Caucasians, the reduced function PTGS1 -1006A variant allele was significantly more common among stroke cases compared to non-cases (18.2 versus 10.6%, P=0.027). In African Americans, the reduced function PTGS2 -765C variant allele was significantly more common in stroke cases (61.4 versus 49.4%, P=0.032). No significant relationships with CHD risk were observed. However, aspirin utilization appeared to modify the relationship between the PTGS2 G-765C polymorphism and CHD risk (interaction P=0.072). These findings suggest that genetic variation in PTGS1 and PTGS2 may be important risk factors for the development of cardiovascular disease events. Confirmation in independent populations is necessary.

DOI10.1038/sj.clpt.6100221
Alternate JournalClin Pharmacol Ther
PubMed ID17495879
PubMed Central IDPMC2244790
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
F32 ES012856-02 / ES / NIEHS NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
R01 HL073366 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
ES012856 / ES / NIEHS NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
F32 ES012856-03 / ES / NIEHS NIH HHS / United States
F32 ES012856-01 / ES / NIEHS NIH HHS / United States
/ / Intramural NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
HL073366 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
F32 ES012856 / ES / NIEHS NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States