Submitted to: Pharmacotherapy
Publication Type: Abstract Only
Publication Acceptance Date: 10/4/2006
Publication Date: 11/29/2006
Citation: Lee, C.R., North, K.E., Bray, M.S., Couper, D.J., Heiss, G., Zeldin, D.C. 2006. The G-765C promoter polymorphism in cyclooxygenase-2 (PTGS2), aspirin utilization and cardiovascular disease risk: the Athrosclerosis Risk in Communities (ARIC) study [abstract]. Pharmacotherapy. 26(Suppl):e87. Interpretive Summary:
Technical Abstract: Cyclooxygenase-2 derived prostaglandins modulate cardiovascular disease risk. We sought to determine if the reduced function G-765C promoter polymorphism in PTGS2 was associated with incident coronary heart disease (CHD) or ischemic stroke risk, and if this was modified by aspirin utilization. Using a case-cohort design, 2275 participants (73% Caucasian) of the biethnic, multicenter ARIC study [all incident CHD (n=1085) and ischemic stroke (n=300) cases occurring from 1987-98; 958 noncases from a cohort representative sample] were genotyped for the G-765C polymorphism. Associations between genotype and risk of incident CHD and ischemic stroke events were evaluated by proportional hazards regression with covariate adjustment. All analyses were race stratified. The putative interaction between baseline aspirin utilization (yes/no) and genotype was assessed in Caucasians, but not African-Americans due to sample size limitations. In African-Americans, presence of at least one variant -765C allele was significantly more common in stroke cases vs. noncases (61.4% vs. 49.4%, P=0.032), and associated with higher incident stroke risk relative to two -765G alleles (adjusted hazard rate ratio (aHRR) 1.76, 95% CI 1.05-2.94, P=0.031). No significant association with incident CHD was observed (aHRR 1.03, 95% CI 0.69-1.52, P=0.894). In Caucasians, no significant association with incident stroke was observed (aHRR 0.79, 95% CI 0.50-1.25, P=0.314). This relationship was not modified by aspirin utilization (P=0.630). No significant association between the -765C allele and CHD risk was observed. This relationship appeared to be modified by aspirin utilization; however, the interaction did not attain statistical significance. The variant -765C allele in PTGS2 was associated with significantly higher ischemic stroke risk in African-Americans. Association between the -765C allele and CHD risk may be modified by aspirin utilization in Caucasians. Confirmatory studies are necessary.