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

Shun Kohsaka, Kelly A. Volcik, Aaron R. Folsom, Kenneth K. Wu, Christie M. Ballantyne, James T. Willerson, Eric Boerwinkle

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)926-930
Number of pages5
Issue number2
StatePublished - Feb 2008

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. The authors thank the staff and participants of the ARIC study for their important contributions.


  • Cerebrovascular accident
  • Coronary disease
  • Cyclooxygenase 2
  • Genetic
  • Polymorphism
  • Risk factors


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