The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

Clappers, Nick; Oijen, Martijn G.H. van; Sundaresan, Santosh; Brouwer, Marc A.; Morsche, R.H.M. te; Keuper, Wessel; Peters, Wilbert H.M.; Drenth, Joost P.H.; Verheugt, Freek W. A.

doi:10.1160/th08-03-0172

Cited by 36 publications

(6 citation statements)

References 10 publications

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“…Further studies are necessary to determine whether PTGS1 genotype correlates with clinical response to aspirin. A recent study found no association between PTGS1 genotype and clinical outcomes during aspirin therapy; however, this study was done in Caucasians [22]. Whether PTGS1 genotype contributes to the ability of aspirin to prevent clinical sequelae in ethnically diverse populations has yet to be determined.…”

Section: Discussionmentioning

confidence: 96%

“…Similarly, a study limited to Caucasians found no association between aspirin response, as measured by clinical thrombotic events, and PTGS1 P17L genotype [22]. Lee et al [13] previously showed that the PTGS1 haplotype structure differs by ethnicity, with significant linkage disequilibrium between the A–707G and P17L variants in Caucasians, but not African Americans.…”

Section: Discussionmentioning

confidence: 99%

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Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

et al. 2009

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Background: We sought to determine whether cyclooxygenase-1 (PTGS1) genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. Methods: Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the PTGS1 A–707G, PTGS1 P17L, and glycoprotein IIIa (ITGB3)P1^A1/A2 genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B₂ (11-dhTxB₂) concentrations. The association between PTGS1 A–707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB₂ concentrations, was evaluated by statistical testing and nonlinear mapping. Results: Salicylate concentrations, ITGB3 genotype distribution and 11-dhTxB₂ concentrations were similar among PTGS1 genotype groups. More subjects with the PTGS1 17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the PTGS –707A and 17P alleles, but none with both the PTGS1 –707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the PTGS1 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians. Conclusions: Our data suggest that the PTGS1 P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between PTGS1 genotype and aspirin response might vary by ethnicity.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

et al. 2009

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“…The COX-1 C50T single-nucleotide polymorphism (SNP) reduces response to aspirin but does not modify the risk of atherothrombotic events in White people. 11,12 In a Swedish cohort, the COX-1 SNP rs883484 TT was associated with increased formation of PGF 2α , while the COX-1 SNP rs10306135 TT was associated with decreased formation of PGF 2α and lower prevalence of CVD. 13 The COX-1 rs1330344 SNP CC genotype is associated with an increased risk of subsequent vascular…”

Section: Cox-1 and Cox-2 In The Cardiovascular Systemmentioning

confidence: 99%

Prostanoids in Cardiac and Vascular Remodeling

Ricciotti,

Haines,

Chai

et al. 2024

ATVB

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Prostanoids are biologically active lipids generated from arachidonic acid by the action of the COX (cyclooxygenase) isozymes. NSAIDs, which reduce the biosynthesis of prostanoids by inhibiting COX activity, are effective anti-inflammatory, antipyretic, and analgesic drugs. However, their use is limited by cardiovascular adverse effects, including myocardial infarction, stroke, hypertension, and heart failure. While it is well established that NSAIDs increase the risk of atherothrombotic events and hypertension by suppressing vasoprotective prostanoids, less is known about the link between NSAIDs and heart failure risk. Current evidence indicates that NSAIDs may increase the risk for heart failure by promoting adverse myocardial and vascular remodeling. Indeed, prostanoids play an important role in modulating structural and functional changes occurring in the myocardium and in the vasculature in response to physiological and pathological stimuli. This review will summarize current knowledge of the role of the different prostanoids in myocardial and vascular remodeling and explore how maladaptive remodeling can be counteracted by targeting specific prostanoids.

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“…4 Some studies suggest that the variability in aspirin response may be due to COX-1 (Prostaglandin-endoperoxide synthase [PTGS1]) genetic variants because they impact platelet function and aspirin response. 10–12 However, there is uncertainty in the genetic effect of COX-1 on stroke outcomes due to a lack of well-powered studies.…”

Section: Aspirinmentioning

confidence: 99%

Pharmacogenomics in Stroke and Cardiovascular Disease: State of the Art

Ross

Krebs

Paré

et al. 2023

Stroke

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There is considerable interindividual variability in the response to antiplatelet and anticoagulant therapies, and this variation may be attributable to genetic variants. There has been an increased understanding of the genetic architecture of stroke and cardiovascular disease, which has been driven by advancements in genomic technologies and this has raised the possibility of more targeted pharmaceutical treatments. Pharmacogenetics promises to use a patient’s genetic profile to treat those who are more likely to benefit from a particular intervention by selecting the best possible therapy. Although there are numerous studies indicating strong evidence for the effect of specific genotypes on the outcomes of vascular drugs, the adoption of pharmacogenetic testing in clinical practice has been slow. This resistance may stem from sometimes conflicting findings among pharmacogenetic studies, a lack of stroke-specific randomized controlled trials to test the effectiveness of genetically-guided therapies, and the practical and cost-effective implementation of genetic testing within the clinic. Thus, this review provides an overview of the genetic variants that influence the individual responses to aspirin, clopidogrel, warfarin and statins and the different methods for pharmacogenetic testing and guidelines for clinical implementation for stroke patients.

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The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

Cited by 36 publications

References 10 publications

Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

Prostanoids in Cardiac and Vascular Remodeling

Pharmacogenomics in Stroke and Cardiovascular Disease: State of the Art

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