Increased risk of incident stroke associated with the cyclooxygenase 2 (COX-2) G−765C polymorphism in African-Americans: The Atherosclerosis Risk in Communities Study

Background A hallmark feature of atherosclerosis is inflammation mediated by prostaglandins (PGs) catalyzed by the enzyme cyclooxygenase (COX). The present study explored whether the COX-2 G−765C polymorphism contributes to increased incidence of coronary heart disease (CHD) or stroke in the large prospective Atherosclerosis Risk in Communities (ARIC) Study. Methods Incidences of CHD and stroke were identified through annual follow-up and hospital and death certificate surveillance. The study included 1488 incident CHD and 527 stroke events after an average of 14 years of follow-up. The frequency of the −765C variant allele was markedly different between African-Americans and whites, therefore all analyses were performed separately by race. Due to the small number of persons with the −765CC genotype, heterozygous and homozygous variant genotypes were combined for this analysis. Results The COX-2 G−765C polymorphism was not a significant predictor of CHD in either racial group, but it was a significant predictor of incident stroke in African-Americans. After adjustment for age and gender, the hazard rate ratio for developing stroke for the CG+CC genotypes relative to the GG genotype was 1.34 (95% confidence interval [CI] 1.03–1.74, P = 0.03) in African-Americans. This result was essentially unchanged when established predictors such as smoking, diabetes and hypertension were added to the model (HRR 1.34, 95%CI 1.03–1.76, P = 0.03). Conclusion We have found the COX-2 G−765C polymorphism to be a risk factor for incident stroke in African-Americans. This study provides additional evidence for utilizing inflammation-related genetic polymorphisms for identifying individuals at increased risk for stroke.