title: Genetic determinants of platelet large-cell ratio, immature platelet fraction, and other platelet-related phenotypes.
abstract: BACKGROUND
  Platelets play a significant role in arterial thrombosis and are involved also in venous thrombosis. The genetic determinants of several platelet-related phenotypes have been studied previously. However, to the best of our knowledge, the genetic determinants of other platelet phenotypes have not been reported such as platelet-large-cell ratio (P-LCR) index, immature platelet fraction (IPF) parameters and overall platelet function measured through the PFA-100 system.
  
  
  METHODS
  As part of the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project, 935 individuals from 35 large Spanish families, ascertained through a proband with thrombophilia, were studied. Using variance component methods, implemented in the SOLAR package, the heritability of the following sets of platelet-related phenotypes was determined: platelet count and indices, IPF, and platelet function.
  
  
  CONCLUSIONS
  High heritabilities of the platelet count and index phenotypes (from 0.41 to 0.64) were found, especially for those related to platelet volume. The heritabilities of the IPF phenotypes, as a measure of platelet turnover, were the highest (from 0.65 to 0.69). The heritabilities of the platelet function phenotypes were high also (0.45 and 0.62). The covariate age influenced all of the platelet phenotypes. Smoking influenced the platelet indices related to platelet volume and all the IPF phenotypes. Venous thrombosis showed a heritability of 0.67. We did not find a genetic correlation between any of the platelet-related phenotypes and venous thrombosis. The high heritabilities found for all of the platelet phenotypes provid promising data for the identification of new genes that underly these phenotypes.
authors.affiliation: Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Spain. Electronic address: npujolmoix@gmail.com.
authors.forename: Núria
authors.initials: N
authors.lastname: Pujol-Moix
authors.affiliation: Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: mvazquezs@santpau.cat.
authors.forename: Miquel
authors.initials: M
authors.lastname: Vázquez-Santiago
authors.affiliation: Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: ambnesi@gmail.com.
authors.forename: Agnès
authors.initials: A
authors.lastname: Morera
authors.affiliation: Unit of Genomics of Complex Diseases, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain. Electronic address: aziyatdinov@santpau.cat.
authors.forename: Andrey
authors.initials: A
authors.lastname: Ziyatdinov
authors.affiliation: Servei de Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: aremacha@santpau.cat.
authors.forename: Angel
authors.initials: A
authors.lastname: Remacha
authors.affiliation: Servei de Laboratori d'Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: jnomdedeu@santpau.cat.
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedeu
authors.affiliation: Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: jfontcuberta@santpau.cat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Fontcuberta
authors.affiliation: Unit of Genomics of Complex Diseases, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain. Electronic address: jsoria@santpau.cat.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Soria
authors.affiliation: Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Electronic address: jsouto@santpau.cat.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Souto
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000145:classification* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D063847:Mean Platelet Volume / Q000706:statistics & numerical data*; D010976:Platelet Count / Q000706:statistics & numerical data*; D015995:Prevalence; D013030:Spain / Q000453:epidemiology; D019851:Thrombophilia / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
keywords: Heritability; Immature platelet fraction; Platelet large-cell ratio; Platelets; Thrombophilia