Submitted to: Clinical Pharmacology and Therapeutics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2007
Publication Date: 1/1/2008
Citation: Lee, C.R., North, K.E., Bray, M.S., Couper, D.J., Heiss, G., Zeldin, D.C. 2008. Cyclooxygenase polymorphisms and risk of cardiovascular events: The Atherosclerosis Risk in Communities (ARIC) study. Clinical Pharmacology and Therapeutics. 83(1):52-60. Interpretive Summary: Variation in DNA sequence can influence the risk of developing disease by altering the genes and proteins encoded by the sequence. This study investigated the relationship between heart disease and DNA sequence variation in two genes, PTGS1 and PTGS2, which influence heart function. Elderly African American and white adults were included in the study. The study found that variation in the DNA sequence of the PTGS1 and PTGS2 genes may increase risk for the development of cardiovascular disease, especially stroke.
Technical 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.