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

Autor: Anders Hamsten, Angel Martinez-Perez, Dolors Llobet, Nuria Pujol-Moix, Joan Carles Souto, Maria Sabater-Lleal, Noelia Vilalta, José Manuel Soria
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
platelet reactivity
Platelet Aggregation
Genome-wide association study
Von Willebrand factor
030204 cardiovascular system & hematology
von Willebrand factor
Genetic analysis
lcsh:Chemistry
0302 clinical medicine
hemic and lymphatic diseases
Thrombophilia
Child
lcsh:QH301-705.5
Spectroscopy
Genetics
Aged
80 and over
biology
ABO blood-group system
General Medicine
Middle Aged
Phenotype
Computer Science Applications
factor VIII
Child
Preschool
Female
Adult
congenital
hereditary
and neonatal diseases and abnormalities
Adolescent
Platelet Function Tests
Locus (genetics)
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
ABO blood group system
parasitic diseases
medicine
Humans
Physical and Theoretical Chemistry
Molecular Biology
Aged
Platelet function test
Factor VIII
Organic Chemistry
medicine.disease
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
platelet function test
Platelet reactivity
Zdroj: Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
International Journal of Molecular Sciences, Vol 20, Iss 13, p 3221 (2019)
International Journal of Molecular Sciences
Volume 20
Issue 13
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname
ISSN: 1422-0067
Popis: (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 &asymp
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.
Databáze: OpenAIRE
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