Abstract 2655: Polymorphisms in the Gene Encoding for Cyclooxygenase-2 and the Risk of Recurrent Atherothrombotic Events
Multiple single nucleotide polymorphisms (SNP’s) in the gene encoding for cyclooxygenase-2 (COX-2) have been identified. These SNP’s may modify risk of atherothrombotic events. The COX-2 -765G->C SNP has been associated with decreased COX-2 activity and with significantly lower odds of a first atherothrombotic event. The −1195G->A SNP on the other hand seems to be correlated with increased COX-2 activity, but has not been investigated in relation to atherothrombotic events. Our aim is to investigate whether these two functional COX-2 SNP’s are associated with the risk of recurrent atherothrombotic events. Patients hospitalized between Apr 2002 and Jan 2004 with acute coronary syndrome were genotyped for the COX-2 −765G->C and −1195G->A SNP’s and followed up to July 2008. The primary endpoint was a composite of cardiovascular death, myocardial infarction and/or stroke. Multivariate analysis was performed. We included a cohort of 379 consecutive patients (median age 66 y (IQR 55–73), 66% were males). Genotyping for the −765G->C showed frequencies of 72% GG, 27% GC and 1% CC. For the −1195G->A frequencies were 5% GG, 35% GA and 60% AA. There was strong linkage disequilibrium (D’=−1.0) between both SNP’s. The primary endpoint occurred in 82 patients (22%). The unadjusted hazard ratio for the −765GC/CC genotypes was 1.33 (95% confidence intervals [CI] 0.84 –2.10, p= 0.22) compared with −765GG, the adjusted hazard ratio was 1.16 (95% CI 0.72–1.88, p=0.54). Haplotype analysis of the combination of −1195- and −765-genotypes, revealed no genetic subgroup at significantly increased risk either. Previously, the COX-2 −765G->C SNP was associated with a reduced risk for first atherothrombotic event. For the risk of recurrent events we found no effect for this SNP. In addition we studied the combination with the functional −1195G->A SNP of COX-2, which did not show a significant effect on recurrent events either.