Polymorphisms in Two Regions of the Cyclo-Oxygenase-2 Gene Associated with Variation in Risk of Coronary Thrombosis with Cyclo-Oxygenase-2 Inhibitors

David A Henry, Lisa F. Lincz, John R. Attia, Patrick McElduff, L Bisset, Roseanne Peel, Stephen Hancock, Kim M. Henderson, Diana Whitaker, Michael Seldon, Patricia McGettigan

Research output: Contribution to journalMeeting AbstractResearchpeer-review

Abstract

Introduction: Genetic factors might explain variations in the relative
risk (RR) of vascular events with non-steroidal anti-inflammatory drugs
(NSAIDs). We investigated variations in RR of acute coronary syndrome
(ACS) with NSAIDs in the presence of two single nucleotide polymorphisms (SNPs;-765G fi C, rs20417 and 6498T fi C, rs5275) in the
cyclo-oxygenase-2 (COX-2) gene.
Patients and Methods: Cases (n = 460) were hospitalized with ACS.
Controls (n = 640) were recruited from the electoral roll. Structured
interviews gathered information on variables including ingestion of selective COX-2 inhibitors and other NSAIDs. Genotyping was performed by
real-time PCR using allele-specific probes. Relative risks were estimated
from exposure odds ratios (ORs) using multiple logistic regression in the
presence and absence of polymorphisms.
Results: Overall, ingestion of any NSAID in the week prior to interview
was associated with an elevated RR for ACS (1.55; 95% CI 1.16, 2.06).
Individually, the -765G fi C and 6498T fi C SNPs were not associated
with significant variations in the risk for ACS with either COX-2 inhibitors or all NSAIDs. When analysis was conducted by haplotype, OR
with COX-2 inhibitors in the presence of the minor alleles (-765C and
6498C) was 1.01 (0.25, 4.16), compared with 2.38 (1.29, 4.39) in the
presence of one or two copies of either of the more common alleles
(-765G and/or 6498T). A similar effect was seen with use of any
NSAID: 1.60 (0.65, 3.93) vs. 2.17 (1.30, 3.63), respectively
Conclusions: These polymorphisms may affect COX-2 enzyme levels
and explain some inter-individual variation in risk of coronary occlusion
with NSAIDs.
Original languageEnglish
Article numberO64
Pages (from-to)39
JournalBasic and Clinical Pharmacology and Toxicology
Volume105
Issue numberS1
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

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