The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene

Patricia McGettigan, Lisa F. Lincz, John R. Attia, Patrick McElduff, Linda Bissett, Roseanne Peel, Barrie J. Stokes, Stephen Hancock, Kim Henderson, Michael Seldon, David Henry*

*Corresponding author for this work

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7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)707-714
Number of pages8
JournalBritish Journal of Clinical Pharmacology
Volume72
Issue number4
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

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Coronary Thrombosis
Cyclooxygenase Inhibitors
Prostaglandin-Endoperoxide Synthases
Haplotypes
Acute Coronary Syndrome
Genes
Anti-Inflammatory Agents
Celecoxib
Odds Ratio
Pharmaceutical Preparations
Eating
Interviews
South Australia
New South Wales
Drug Interactions
Case-Control Studies
Real-Time Polymerase Chain Reaction
Alleles

Cite this

McGettigan, Patricia ; Lincz, Lisa F. ; Attia, John R. ; McElduff, Patrick ; Bissett, Linda ; Peel, Roseanne ; Stokes, Barrie J. ; Hancock, Stephen ; Henderson, Kim ; Seldon, Michael ; Henry, David. / The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene. In: British Journal of Clinical Pharmacology. 2011 ; Vol. 72, No. 4. pp. 707-714.
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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",
abstract = "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.",
author = "Patricia McGettigan and Lincz, {Lisa F.} and Attia, {John R.} and Patrick McElduff and Linda Bissett and Roseanne Peel and Stokes, {Barrie J.} and Stephen Hancock and Kim Henderson and Michael Seldon and David Henry",
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The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene. / McGettigan, Patricia; Lincz, Lisa F.; Attia, John R.; McElduff, Patrick; Bissett, Linda; Peel, Roseanne; Stokes, Barrie J.; Hancock, Stephen; Henderson, Kim; Seldon, Michael; Henry, David.

In: British Journal of Clinical Pharmacology, Vol. 72, No. 4, 10.2011, p. 707-714.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - The risk of coronary thrombosis with cyclo-oxygenase-2 inhibitors does not vary with polymorphisms in two regions of the cyclo-oxygenase-2 gene

AU - McGettigan, Patricia

AU - Lincz, Lisa F.

AU - Attia, John R.

AU - McElduff, Patrick

AU - Bissett, Linda

AU - Peel, Roseanne

AU - Stokes, Barrie J.

AU - Hancock, Stephen

AU - Henderson, Kim

AU - Seldon, Michael

AU - Henry, David

PY - 2011/10

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N2 - 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.

AB - 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.

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