Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.

Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide...

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Main Authors: Morten Würtz, Peter H Nissen, Erik Lerkevang Grove, Steen Dalby Kristensen, Anne-Mette Hvas
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4216141?pdf=render
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spelling doaj-4099ecaa2b0e4d2d9580ef87b9c9cf732020-11-24T20:50:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11181610.1371/journal.pone.0111816Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.Morten WürtzPeter H NissenErik Lerkevang GroveSteen Dalby KristensenAnne-Mette HvasPlatelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.ClinicalTrials.gov NCT01383304.http://europepmc.org/articles/PMC4216141?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Morten Würtz
Peter H Nissen
Erik Lerkevang Grove
Steen Dalby Kristensen
Anne-Mette Hvas
spellingShingle Morten Würtz
Peter H Nissen
Erik Lerkevang Grove
Steen Dalby Kristensen
Anne-Mette Hvas
Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.
PLoS ONE
author_facet Morten Würtz
Peter H Nissen
Erik Lerkevang Grove
Steen Dalby Kristensen
Anne-Mette Hvas
author_sort Morten Würtz
title Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.
title_short Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.
title_full Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.
title_fullStr Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.
title_full_unstemmed Genetic determinants of on-aspirin platelet reactivity: focus on the influence of PEAR1.
title_sort genetic determinants of on-aspirin platelet reactivity: focus on the influence of pear1.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description Platelet aggregation during aspirin treatment displays considerable inter-individual variability. A genetic etiology likely exists, but it remains unclear to what extent genetic polymorphisms determine platelet aggregation in aspirin-treated individuals.To identify platelet-related single nucleotide polymorphisms (SNPs) influencing platelet aggregation during aspirin treatment. Furthermore, we explored to what extent changes in cyclooxygenase-1 activity and platelet activation may explain such influence.We included 985 Danish patients with stable coronary artery disease treated with aspirin 75 mg/day mono antiplatelet therapy. Patients were genotyped for 16 common SNPs in platelet-related genes using standard PCR-based methods (TaqMan). Platelet aggregation was evaluated by whole blood platelet aggregometry employing Multiplate Analyzer (agonists: arachidonic acid and collagen) and VerifyNow Aspirin. Serum thromboxane B2 was measured to confirm aspirin adherence and was used as a marker of cyclooxygenase-1 activity. Soluble P-selectin was used as marker of platelet activation. Platelet aggregation, cyclooxygenase-1 activity, and platelet activation were compared across genotypes in adjusted analyses.The A-allele of the rs12041331 SNP in the platelet endothelial aggregation receptor-1 (PEAR1) gene was associated with reduced platelet aggregation and increased platelet activation, but not with cyclooxygenase-1 activity. Platelet aggregation was unaffected by the other SNPs analyzed.A common genetic variant in PEAR1 (rs12041331) reproducibly influenced platelet aggregation in aspirin-treated patients with coronary artery disease. The exact biological mechanism remains elusive, but the effect of this polymorphism may be related to changes in platelet activation. Furthermore, 14 SNPs previously suggested to influence aspirin efficacy were not associated with on-aspirin platelet aggregation.ClinicalTrials.gov NCT01383304.
url http://europepmc.org/articles/PMC4216141?pdf=render
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