title: Role of the T744C polymorphism of the P2Y12 gene on platelet response to a 600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome.
abstract: BACKGROUND
  Variability in platelet response to clopidogrel and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. Recently, the T744C polymorphism of the P2Y12 receptor gene has been associated with enhanced platelet aggregation in healthy volunteers, suggesting a possible mechanism for modulation of clopidogrel response.
  
  
  OBJECTIVE
  To assess whether the clopidogrel response may be influenced by the T744C P2Y12 gene polymorphism in patients with non ST elevation acute coronary syndrome (NSTE ACS).
  
  
  METHODS
  597 NSTE ACS patients were included in our study and were divided into 3 groups: CC homozygotes, CT heterozygotes ad TT homozygotes. All patients received loading doses of 600 mg clopidogrel and 250 mg aspirin at least 12 hours before blood samples. Clopidogrel response was assessed by post-treatment ADP 10 micromol/L-induced platelet aggregation (ADP-Ag), VASP phosphorylation (PRI VASP) and P-selectin expression (PS). Clopidogrel resistance was defined by persistence of High Post-treatment Platelet Reactivity (HPPR=ADP-Ag>70%).
  
  
  RESULTS
  Significant variability in the distribution of platelet parameters was observed in the overall study population. No significant difference in platelet parameter profiles was observed within patients having the same genotype, for ADP-Ag (p=0.39), PRI VASP (p=0.97) and PS (p=0.62). The genotype frequencies of the T744C polymorphism of the P2Y12 gene were similar in responders and non responders defining by HPPR (p=0.75).
  
  
  CONCLUSIONS
  Our study did not show any influence of the T744C polymorphism of the P2Y12 receptor gene on clopidogrel response assessed by ADP-Ag, PRI VASP or P-selectin expression in NSTE ACS patients.
authors.affiliation: Department of Cardiology, CHU Timone, Marseille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cuisset
authors.forename: Corinne
authors.initials: C
authors.lastname: Frere
authors.forename: Jacques
authors.initials: J
authors.lastname: Quilici
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: Noémie
authors.initials: N
authors.lastname: Saut
authors.forename: Marc
authors.initials: M
authors.lastname: Lambert
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin
authors.forename: Irène Juhan
authors.initials: IJ
authors.lastname: Vague
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bonnet
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
mesh_terms: D000208:Acute Disease; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D000077144:Clopidogrel; D004351:Drug Resistance / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006331:Heart Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D019007:P-Selectin; C548576:P2RY12 protein, human; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine