Key result
The A-allele of the PEAR1 rs12041331 polymorphism was significantly associated with reduced on-aspirin platelet aggregation (p<0.0001) in patients with stable coronary artery disease.
Why the study?
Does the PEAR1 rs12041331 polymorphism influence platelet aggregation in aspirin-treated patients with stable coronary artery disease?
Cross-Sectional (n=985)
Yes
Does the PEAR1 rs12041331 polymorphism influence platelet aggregation in aspirin-treated patients with stable coronary artery disease?
The PEAR1 rs12041331 genetic variant is associated with reduced platelet aggregation in aspirin-treated CAD patients, suggesting a genetic basis for inter-individual variability in aspirin response.
Does not support PEAR1 testing to guide aspirin therapy; hypothesis-generating for genetic variability in stable CAD.
BACKGROUND: 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. AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01383304.
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Würtz et al. (2014) conducted a cross-sectional in Stable coronary artery disease (n=985). PEAR1 rs12041331 A-allele vs. PEAR1 rs12041331 GG genotype was evaluated on Platelet aggregation evaluated one hour after aspirin intake (p=<0.0001). The A-allele of the PEAR1 rs12041331 polymorphism was significantly associated with reduced on-aspirin platelet aggregation (p<0.0001) in patients with stable coronary artery disease.
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