title: Genetic variants that affect platelet function.
abstract: OBJECTIVE
  This review summarizes our current knowledge of common gene variants (polymorphisms) that have small individual effects on platelet function in humans, but can cumulatively lead to hyperreactive platelets and increase risk for negative outcomes in thrombotic disorders.
  
  
  RESULTS
  Candidate gene association and genome-wide association studies (GWAS) have identified loci that include single nucleotide polymorphisms, which exert a cumulative effect on platelet function by modifying basic platelet parameters, such as mean platelet volume (MPV) or platelet count, by altering the expression or activity of key platelet receptors, or by influencing downstream effector pathways utilized by these receptors.
  
  
  CONCLUSIONS
  Variation in MPV between normal individuals is responsible for roughly a two-fold range in platelet protein content, including key surface receptors and reactive granule constituents, the association of ADRA2, GP1BA, GP6, ITGA2 and P2Y12 variants with platelet reactivity, initially identified by candidate gene analyses, has now been validated by genome-wide approaches in much larger individual cohorts, and GWAS have identified novel gene variants, most notably PEAR1, that participate in variation in platelet reactivity among normal individuals, all of which contribute to a genetic basis for differences in platelet reactivty among normal individuals.
authors.affiliation: Hematology Research, CHOC Children's Hospital, University of California, Irvine, Orange, USA. tkunicki@choc.org
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kunicki
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Williams
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Nugent
mesh_terms: D001792:Blood Platelets / Q000502:physiology*; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006801:Humans; D010976:Platelet Count; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface