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- Title
The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene.
- Authors
McGettigan, Patricia; Lincz, Lisa F.; Attia, John; McElduff, Patrick; Bissett, Linda; Peel, Roseanne; Stokes, Barrie; Hancock, Stephen; Henderson, Kim; Seldon, Michael; Henry, David
- Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The risk of cardiovascular events with non-steroidal anti-inflammatory drugs (NSAIDs) varies with individual drugs and with dosage. Little is known about other factors that can modify risk. • Polymorphisms of the COX-2 gene conceivably could alter the risk of myocardial infarction and also the risk from NSAIDs. WHAT THIS STUDY ADDS • Two common polymorphisms of the COX-2 gene, rs 20417 (G > C) and rs 5275 (T > C), were not associated with variation in the risk of acute coronary syndrome, and individually did not alter the risk associated with use of NSAIDs. • Haplotype analysis identified a trend to protection against NSAID-related cardiovascular risk with the 'low risk' haplotype, but the effect was weak and if confirmed, the clinical utility would be limited. AIMS To investigate whether polymorphisms of the cyclo-oxygenase-2 ( COX-2) gene modify the adverse cardiovascular effects of COX-2 inhibitors. METHODS A case control study was conducted in the Hunter Region of New South Wales, Australia. Cases ( n= 460) were hospitalized with acute coronary syndrome (ACS). Controls ( n= 640) were recruited from the electoral rolls. Structured interviews gathered information on variables including recent ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). Targeted genotyping of rs 20417(G > C) and rs5275 (T > C) polymorphisms was performed by real-time polymerase chain reaction using allele-specific probes RESULTS Ingestion of any NSAID in the week prior to interview was associated with an elevated risk for ACS: adjusted odds ratio 1.8 (1.2, 2.5). The rs 20417 and rs 5275 polymorphisms were not singly associated with risk for ACS: adjusted odds ratios 1.1 (0.80, 1.5) and 1.2 (0.88, 1.5), respectively. Individually, the polymorphisms did not modify the risk of ACS with the drugs. When analyses were conducted by haplotype, the adjusted odds ratio with celecoxib or rofecoxib in individuals who had one or two copies of the 'low risk' haplotype (no GT) was 1.2 (0.29, 5.0), compared with 2.1 (1.1, 4.0) with the 'high risk' haplotype (one or two copies of GT). CONCLUSIONS We found little evidence of a gene/drug interaction. We found a statistically non-significant trend toward a lower risk of coronary events with NSAIDs in the presence of the 'low risk' haplotype. Even if confirmed, the clinical utility of the finding would be limited as this haplotype is carried by a minority of the population.
- Subjects
NEW South Wales; NONSTEROIDAL anti-inflammatory agents; GENETIC polymorphisms; MYOCARDIAL infarction; ACUTE coronary syndrome; POLYMERASE chain reaction
- Publication
British Journal of Clinical Pharmacology, 2011, Vol 72, Issue 4, p707
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/j.1365-2125.2011.03957.x