Influence of ABO locus on PFA-100 collagen-ADP closure time is not totally dependent on the von willebrand factor. Results of a GWAS on gait-2 project phenotypes

Núria Pujol-Moix, Angel Martinez-Perez, Maria Sabater-Lleal, Dolors Llobet, Noèlia Vilalta, Anders Hamsten, Joan Carles Souto, José Manuel Soria

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    Abstract

    © 2019 by the authors. Licensee MDPI, Basel, Switzerland. (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 ABO locus. After adjusting both phenotypes for the ABO 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 ABO locus exerts the main genetic influence on PFA-100 phenotypes. However, while the effect of the ABO locus on Col-Epi phenotype is mediated through VWF and/or FVIII, the effect of the ABO locus on Col-ADP phenotype is partly produced through VWF and/or FVIII, and partly through other mechanisms.
    Original languageEnglish
    Article number3221
    JournalInternational Journal of Molecular Sciences
    Volume20
    DOIs
    Publication statusPublished - 1 Jul 2019

    Keywords

    • ABO blood-group system
    • Factor VIII
    • Platelet function test
    • Platelet reactivity
    • Von Willebrand factor

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    Pujol-Moix, N., Martinez-Perez, A., Sabater-Lleal, M., Llobet, D., Vilalta, N., Hamsten, A., Souto, J. C., & Soria, J. M. (2019). Influence of ABO locus on PFA-100 collagen-ADP closure time is not totally dependent on the von willebrand factor. Results of a GWAS on gait-2 project phenotypes. International Journal of Molecular Sciences, 20, [3221]. https://doi.org/10.3390/ijms20133221