Key result
Aspirin administration at therapeutic doses altered platelet aggregation in a pathway-specific manner dependent on PEAR1 rs12041331 genotype, affecting collagen and epinephrine pathways (P<0.05).
Why the study?
Does PEAR1 rs12041331 genotype affect agonist-induced platelet aggregation before and after aspirin administration in healthy individuals?
Cohort (n=67)
Does PEAR1 rs12041331 genotype affect agonist-induced platelet aggregation before and after aspirin administration in healthy individuals?
The PEAR1 rs12041331 genetic variant affects platelet aggregation in a pathway-specific manner that is altered by therapeutic doses of aspirin.
PEAR1 genotyping may inform aspirin response; leaves open need for outcome trials before guiding therapy in patients.
Genetic variation in the platelet endothelial aggregation receptor 1 (PEAR1) gene, most notably rs12041331, is implicated in altered on-aspirin platelet aggregation and increased cardiovascular event risk. We prospectively tested the effects of aspirin administration at commonly prescribed doses (81, 162, and 324 mg/day) on agonist-induced platelet aggregation by rs12041331 genotype in 67 healthy individuals. Prior to aspirin administration, rs12041331 minor allele carriers had significantly reduced adenosine diphosphate (ADP)-induced platelet aggregation compared with noncarriers (P = 0.03) but was not associated with other platelet pathways. In contrast, rs12041331 was significantly associated with on-aspirin platelet aggregation when collagen and epinephrine were used to stimulate platelet aggregation (P < 0.05 for all associations), but not ADP. The influence of PEAR1 rs12041331 on platelet aggregation is pathway-specific and is altered by aspirin at therapeutic doses, but not in a dose-dependent manner. Additional studies are needed to determine the impact of PEAR1 on cardiovascular events in aspirin-treated patients.
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Backman et al. (2017) conducted a cohort in Healthy individuals (n=67). Aspirin vs. rs12041331 noncarriers was evaluated on Agonist-induced platelet aggregation (p=<0.05). Aspirin administration at therapeutic doses altered platelet aggregation in a pathway-specific manner dependent on PEAR1 rs12041331 genotype, affecting collagen and epinephrine pathways (P<0.05).
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