Abstract 15111: Genome-Wide Association Study Links Variants With Occurrence of Cardiovascular Events in People Taking the COX-2 Inhibitor Celecoxib: Identification of NCKX2 as a Novel Protective Pathway in Renal Vessels

Nonsteroidal anti-inflammatory analgesic drugs (NSAIDs) work by blocking cyclooxygenase(COX)-2 and are amongst the most commonly taken drugs worldwide. However they cause cardiovascular adverse events, which because of their widespread use, are of global concern and mean that NSAID usage is a cardiovascular risk factor in its own right. Whilst current research indicates the cardiovascular adverse events are mediated by blocking COX-2 in the kidney and/or blood vessels, no causal genetic variants or detailed mechanistic pathways are known. We have performed a first of its kind genome-wide association study using data from a unique set of ~1000 samples from participants in the Adenoma Prevention with Celecoxib (APC) trial (NEJM; DOI: 10.1056/NEJMoa050405). From individuals taking 200 or 400-mg/day celecoxib, genotype data of 68 cases with cardiovascular events were compared with 959 controls with no events. 4 loci exceeded a nominal discovery p-value threshold of 10-6, but do not predict general cardiovascu...