P2Y12 gene H2 haplotype is not associated with increased adenosine diphosphate-induced platelet aggregation after initiation of clopidogrel therapy with a high loading dose

Blood Coagul Fibrinolysis. 2005 Apr;16(3):199-204. doi: 10.1097/01.mbc.0000164429.21040.0a.

Abstract

A large variability in the antiplatelet response to clopidogrel has been consistently reported. Recently, a P2Y12 haplotype was shown to be associated with enhanced adenosine diphosphate (ADP)-induced platelet aggregation in healthy volunteers. The aim of this study was to test in patients (n = 416) scheduled for coronary artery stenting whether P2Y12 haplotype H2 carriage is associated with increased ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Blood was drawn from the arterial sheath at least 2 h after administration of 100 mg aspirin and 600 mg clopidogrel. ADP-induced platelet aggregation was assessed in platelet-rich plasma with light-transmission aggregometry. P2Y12 haplotypes (H1/H2) and P2Y12 C32T genotypes were determined with TaqMan assays. Haplotype combinations and genotypes were not associated with parameters of ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Maximal ADP (5 mumol/l)-induced platelet aggregation was similar in patients carrying haplotype H2 and homozygous carriers of haplotype H1 (43.9 +/- 21.4 versus 43.2 +/- 21.1%, respectively; P = 0.77). Carriage of P2Y12 H2 haplotype does not seem to affect the platelet response to a 600 mg loading dose of clopidogrel in coronary artery disease patients prior to stenting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology*
  • Aged
  • Aspirin / administration & dosage
  • Clopidogrel
  • Coronary Disease / drug therapy
  • Female
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation / physiology
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2Y12
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Membrane Proteins
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Cell Surface
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine
  • Aspirin