title: The GNB3 C825T polymorphism influences platelet aggregation in human whole blood.
abstract: BACKGROUND
  Platelet aggregation varies among individuals; and genetic factors may alter platelet activation through G-protein-coupled receptors, thus influencing results of point-of-care platelet aggregometry in whole blood. We tested the hypothesis that the C825T polymorphism of the gene GNB3 encoding the G-protein β-3 subunit and the platelet GPIIIa Pl(A1)/(A2) polymorphism of the glycoprotein IIIa influence platelet aggregation.
  
  
  METHODS
  Evoked [thrombin receptor activating peptide (TRAP), ADP, TXA(2) agonist U46619, epinephrine, and collagen] platelet aggregation in whole blood was measured using impedance aggregometry (Multiplate) in 143 healthy individuals (age: 40.2 years ±11.7 SD). Genotypes were determined using pyrosequencing and restriction analysis. Data were analyzed by linear one-way analysis of variance and Student's t-test, linear and multiple regression, and the χ(2)-test, as appropriate.
  
  
  RESULTS
  Homozygous carriers of the GNB3 825C-allele showed significantly (P≤0.022) increased maximum aggregation for EC(75) dosages compared with CT and TT genotypes [e.g. ADP: CC 150±36 vs. TT 126±33 aggregation unit (AU); thrombin receptor activating peptide: CC 175±46 vs. TT 150±38 AU; U46619: CC 164±33 vs. 149±32 AU; epinephrine: CC 66±41 vs. TT 48±34 AU]. In contrast, genotypes of glycoprotein IIb/IIIa PI(A)-polymorphism had no effect. Regression analysis revealed the GNB3 C825T polymorphism as an independent factor for enhanced platelet aggregation, besides factors such as female sex and blood cell values.
  
  
  CONCLUSIONS
  In human whole blood, the GNB3 825CC genotype is associated with enhanced platelet aggregation.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital, University of Duisburg-Essen, Essen, Germany. fabian.dusse@uk-essen.de
authors.forename: Fabian
authors.initials: F
authors.lastname: Dusse
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Frey
authors.forename: Adisa
authors.initials: A
authors.lastname: Bilalic
authors.forename: Daniel
authors.initials: D
authors.lastname: Dirkmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Görlinger
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000483:Alleles; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000097:blood / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D039661:Integrin beta3 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects / Q000378:metabolism; D018179:Receptors, Thrombin / Q000187:drug effects / Q000378:metabolism
chemical_list: C454420:G-protein beta3 subunit; D039661:Integrin beta3; D010446:Peptide Fragments; D058925:Receptors, Purinergic P2Y12; D018179:Receptors, Thrombin; C086309:thrombin receptor peptide SFLLRNP; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D020962:Heterotrimeric GTP-Binding Proteins; D004837:Epinephrine