Find in Library

(1) Background: In a previous study, we found that two phenotypes related to platelet reactivity, measured with the PFA-100 system, were highly heritable. The aim of the present study was to identify genetic determinants that influence the variability of these phenotypes: closure time of collagen-ADP (Col-ADP) and of collagen-epinephrine (Col-Epi). (2) Methods: As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia (2) Project, 935 individuals from 35 large Spanish families were studied. A genome-wide association study (GWAS) with ≈ 10 M single nucleotide polymorphisms (SNPs) was carried out with Col-ADP and Col-Epi phenotypes. (3) Results: The study yielded significant genetic signals that mapped to the <i>ABO</i> locus. After adjusting both phenotypes for the <i>ABO</i> genotype, these signals disappeared. After adjusting for von Willebrand factor (VWF) or for coagulation factor VIII (FVIII), the significant signals disappeared totally for Col-Epi phenotype but only partially for Col-ADP phenotype. (4) Conclusion: Our results suggest that the <i>ABO</i> locus exerts the main genetic influence on PFA-100 phenotypes. However, while the effect of the <i>ABO</i> locus on Col-Epi phenotype is mediated through VWF and/or FVIII, the effect of the <i>ABO</i> locus on Col-ADP phenotype is partly produced through VWF and/or FVIII, and partly through other mechanisms.