Abstract 399: A Novel Variant in the Platelet Endothelial Aggregation Receptor-1 Gene is Associated with Decreased Response to Aspirin
Background: A platelet transmembrane receptor (PEAR1) was recently identified in a search for novel membrane proteins that become activated during platelet aggregation. PEAR1 is thought to be important in platelet contact-induced activation, but its role in agonist-induced platelet activation or in the responsiveness to the inhibitory effect of aspirin (ASA) have not been defined. In addition, genetic variations in the PEAR1 gene and associated platelet phenotypes have not been reported.
Methods: To evaluate the role of PEAR1 signaling in platelet aggregation and ASA responsiveness, we measured platelet aggregation in platelet rich plasma to 2 different agonists, both at baseline and after 2 weeks of ASA (81 mg/day) in 1844 apparently healthy family members of people with premature coronary artery disease (CAD); mean age was 47±13; 55% were women, and 37% Black. Ten single nucleotide polymorphisms (SNPs) were selected to optimize coverage of the gene at a 4 kb density and were genotyped using the Illumina platform. Phenotype-genotype associations were examined by race using a multivariable generalized linear model adjusted for sex, age, known CAD risk factors, fibrinogen, and nonindependence within families using generalized estimating equations.
Results: The SNP rs2768759 [A/C] was a common variant and demonstrated significant associations with agonist-induced platelet activation in two pathways following ASA, but not at baseline. The “A” allele was associated with less platelet aggregation in both Blacks and Whites (Table⇓). The “A” allele frequency was markedly different by race, 0.8 in Blacks and 0.3 in Whites.
Conclusion: These data suggest that the “A” allele is associated with less platelet aggregation following ASA therapy, perhaps causally related to a diminished platelet to platelet interaction via the PEAR1 receptor in both Blacks and Whites.