Cyclooxygenase Polymorphisms and Risk of Cardiovascular Events: The Atherosclerosis Risk in Communities (ARIC) Study

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. Clinical Pharmacology & Therapeutics (2008) 83, 52–60; doi:10.1038/sj.clpt.6100221; published online 9 May 2007