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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Coronary Thrombosis
Cyclooxygenase Inhibitors
Prostaglandin-Endoperoxide Synthases
Polymorphism
Anti-Inflammatory Agents
Genes
Acute Coronary Syndrome
Cyclooxygenase 2 Inhibitors
Pharmaceutical Preparations
Single Nucleotide Polymorphism
Alleles
Eating
Oxygenases
Haplotypes
Blood Vessels
Logistics
Nucleotides
Logistic Models
Odds Ratio
Polymerase Chain Reaction

Cite this

Henry, David A ; Lincz, Lisa F. ; Attia, John R. ; McElduff, Patrick ; Bisset, L ; Peel, Roseanne ; Hancock, Stephen ; Henderson, Kim M. ; Whitaker, Diana ; Seldon, Michael ; McGettigan, Patricia. / Polymorphisms in Two Regions of the Cyclo-Oxygenase-2 Gene Associated with Variation in Risk of Coronary Thrombosis with Cyclo-Oxygenase-2 Inhibitors. In: Basic and Clinical Pharmacology and Toxicology. 2009 ; Vol. 105, No. S1. pp. 39.
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title = "Polymorphisms in Two Regions of the Cyclo-Oxygenase-2 Gene Associated with Variation in Risk of Coronary Thrombosis with Cyclo-Oxygenase-2 Inhibitors",
abstract = "Introduction: Genetic factors might explain variations in the relativerisk (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 thecyclo-oxygenase-2 (COX-2) gene.Patients and Methods: Cases (n = 460) were hospitalized with ACS.Controls (n = 640) were recruited from the electoral roll. Structuredinterviews gathered information on variables including ingestion of selective COX-2 inhibitors and other NSAIDs. Genotyping was performed byreal-time PCR using allele-specific probes. Relative risks were estimatedfrom exposure odds ratios (ORs) using multiple logistic regression in thepresence and absence of polymorphisms.Results: Overall, ingestion of any NSAID in the week prior to interviewwas 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 associatedwith significant variations in the risk for ACS with either COX-2 inhibitors or all NSAIDs. When analysis was conducted by haplotype, ORwith COX-2 inhibitors in the presence of the minor alleles (-765C and6498C) was 1.01 (0.25, 4.16), compared with 2.38 (1.29, 4.39) in thepresence of one or two copies of either of the more common alleles(-765G and/or 6498T). A similar effect was seen with use of anyNSAID: 1.60 (0.65, 3.93) vs. 2.17 (1.30, 3.63), respectivelyConclusions: These polymorphisms may affect COX-2 enzyme levelsand explain some inter-individual variation in risk of coronary occlusionwith NSAIDs.",
author = "Henry, {David A} and Lincz, {Lisa F.} and Attia, {John R.} and Patrick McElduff and L Bisset and Roseanne Peel and Stephen Hancock and Henderson, {Kim M.} and Diana Whitaker and Michael Seldon and Patricia McGettigan",
year = "2009",
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language = "English",
volume = "105",
pages = "39",
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Polymorphisms in Two Regions of the Cyclo-Oxygenase-2 Gene Associated with Variation in Risk of Coronary Thrombosis with Cyclo-Oxygenase-2 Inhibitors. / Henry, David A; Lincz, Lisa F.; Attia, John R.; McElduff, Patrick; Bisset, L; Peel, Roseanne; Hancock, Stephen; Henderson, Kim M.; Whitaker, Diana; Seldon, Michael; McGettigan, Patricia.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 105, No. S1, O64, 08.2009, p. 39.

Research output: Contribution to journalMeeting AbstractResearchpeer-review

TY - JOUR

T1 - Polymorphisms in Two Regions of the Cyclo-Oxygenase-2 Gene Associated with Variation in Risk of Coronary Thrombosis with Cyclo-Oxygenase-2 Inhibitors

AU - Henry, David A

AU - Lincz, Lisa F.

AU - Attia, John R.

AU - McElduff, Patrick

AU - Bisset, L

AU - Peel, Roseanne

AU - Hancock, Stephen

AU - Henderson, Kim M.

AU - Whitaker, Diana

AU - Seldon, Michael

AU - McGettigan, Patricia

PY - 2009/8

Y1 - 2009/8

N2 - Introduction: Genetic factors might explain variations in the relativerisk (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 thecyclo-oxygenase-2 (COX-2) gene.Patients and Methods: Cases (n = 460) were hospitalized with ACS.Controls (n = 640) were recruited from the electoral roll. Structuredinterviews gathered information on variables including ingestion of selective COX-2 inhibitors and other NSAIDs. Genotyping was performed byreal-time PCR using allele-specific probes. Relative risks were estimatedfrom exposure odds ratios (ORs) using multiple logistic regression in thepresence and absence of polymorphisms.Results: Overall, ingestion of any NSAID in the week prior to interviewwas 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 associatedwith significant variations in the risk for ACS with either COX-2 inhibitors or all NSAIDs. When analysis was conducted by haplotype, ORwith COX-2 inhibitors in the presence of the minor alleles (-765C and6498C) was 1.01 (0.25, 4.16), compared with 2.38 (1.29, 4.39) in thepresence of one or two copies of either of the more common alleles(-765G and/or 6498T). A similar effect was seen with use of anyNSAID: 1.60 (0.65, 3.93) vs. 2.17 (1.30, 3.63), respectivelyConclusions: These polymorphisms may affect COX-2 enzyme levelsand explain some inter-individual variation in risk of coronary occlusionwith NSAIDs.

AB - Introduction: Genetic factors might explain variations in the relativerisk (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 thecyclo-oxygenase-2 (COX-2) gene.Patients and Methods: Cases (n = 460) were hospitalized with ACS.Controls (n = 640) were recruited from the electoral roll. Structuredinterviews gathered information on variables including ingestion of selective COX-2 inhibitors and other NSAIDs. Genotyping was performed byreal-time PCR using allele-specific probes. Relative risks were estimatedfrom exposure odds ratios (ORs) using multiple logistic regression in thepresence and absence of polymorphisms.Results: Overall, ingestion of any NSAID in the week prior to interviewwas 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 associatedwith significant variations in the risk for ACS with either COX-2 inhibitors or all NSAIDs. When analysis was conducted by haplotype, ORwith COX-2 inhibitors in the presence of the minor alleles (-765C and6498C) was 1.01 (0.25, 4.16), compared with 2.38 (1.29, 4.39) in thepresence of one or two copies of either of the more common alleles(-765G and/or 6498T). A similar effect was seen with use of anyNSAID: 1.60 (0.65, 3.93) vs. 2.17 (1.30, 3.63), respectivelyConclusions: These polymorphisms may affect COX-2 enzyme levelsand explain some inter-individual variation in risk of coronary occlusionwith NSAIDs.

U2 - 10.1111/j.1742-7843.2009.00436.x

DO - 10.1111/j.1742-7843.2009.00436.x

M3 - Meeting Abstract

VL - 105

SP - 39

JO - Pharmacology and Toxicology

JF - Pharmacology and Toxicology

SN - 0901-9928

IS - S1

M1 - O64

ER -