Abstract 15457: The -765G>C Polymorphism in the Gene Encoding for Cyclooxygenase-2 Increases the Risk for Atherothrombotic Events in Patients with Coronary Artery Disease: A Prospective One-Year Follow-Up Study

Abstract

Background A single nucleotide polymorphism (SNP) known as -765G>C is known to reduce the expression of cyclooxygenase-2 (COX-2). With regard to the effect of this SNP on cardiovascular risk, contrasting results have been reported. Our aim is to investigate whether this functional COX-2 -765G>C SNP is associated with atherothrombotic events in patients with angiographically proven coronary artery disease.

Methods Patients with established coronary artery disease undergoing elective percutaneous coronary intervention between Dec 2005 and Dec 2007 were genotyped for the COX-2 -765G>C SNP and followed up for one year. We dichotomized the population according to genotype: one group of patients with the -765GG genotype and one group with the -765GC/CC genotypes. The primary endpoint was a composite of cardiovascular death, nonfatal acute myocardial infarction, stent thrombosis and/or ischemic stroke. Multivariate analysis was performed.

Results We included a cohort of 997 consecutive patients with available genetic data (mean age 64±11 yrs, 75% were males). Genotyping for the -765G>C showed frequencies of 74% GG, 23% GC and 3% CC. The primary endpoint occurred in 68 patients (6.8%). The unadjusted hazard ratio for the -765GC/CC genotypes was 1.84 (95% confidence intervals [CI] 1.13-3.00, p= 0.015) compared with -765GG, the adjusted hazard ratio was 1.81 (95% CI 1.11-2.95, p=0.018).

Conclusion This one year follow-up study indicates that the COX-2 -765G>C SNP is associated with a significantly increased risk for atherothrombotic events in patients after elective PCI. Our data contribute to the body of conflicting evidence and warrant the incorporation of mechanistic substudies in large clinical cohorts, to further elucidate these discrepant findings.