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
Pujol-Moix, N. (Universitat Autònoma de Barcelona. Departament de Medicina)
Martinez-Perez, Angel (Institut d'Investigació Biomèdica Sant Pau)
Sabater-Lleal, Maria (Karolinska Institutet (Estocolm, Suècia))
Llobet, D. (Institut d'Investigació Biomèdica Sant Pau)
Vilalta, N. (Institut d'Investigació Biomèdica Sant Pau)
Hamsten, Anders (Karolinska Institutet (Estocolm, Suècia))
Souto, J. C. (Institut d'Investigació Biomèdica Sant Pau)
Soria, J. M. (Institut d'Investigació Biomèdica Sant Pau)

Date:	2019
Abstract:	(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.
Grants:	Instituto de Salud Carlos III CP17-00142 Ministerio de Educación, Cultura y Deporte SAF 2008-08159 Ministerio de Economía y Competitividad RD12-0042-0032
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	ABO blood-group system ; Factor VIII ; Platelet function test ; Platelet reactivity ; Von Willebrand factor
Published in:	International journal of molecular sciences, Vol. 20 Núm. 13 (january 2019) , p. 3221, ISSN 1422-0067

DOI: 10.3390/ijms20133221
PMID: 31262040

13 p, 870.8 KB

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