807 C/T Polymorphism of the glycoprotein Ia gene and pharmacogenetic modulation of platelet response to dual antiplatelet treatment

Blood Coagul Fibrinolysis. 2004 Jul;15(5):427-33. doi: 10.1097/01.mbc.0000114439.81125.86.

Abstract

Glycoprotein (GP) Ia/IIa is a major platelet-collagen receptor playing a key role in thrombosis following collagen exposure. The 807 C/T polymorphism of the GP Ia gene (ITGA2) has been associated with platelet GP Ia/IIa receptor expression, having T-allele carriers, increased receptor density and thrombotic risk. The aim of the study was to assess the role of the 807 C/T polymorphism on modulating platelet function in patients undergoing coronary stenting receiving a 300 mg clopidogrel loading dose. Platelet aggregation was assessed in 44 patients by light transmittance aggregometry following adenosine diphosphate and collagen stimuli at baseline, and 10 min, 4 h and 24 h after clopidogrel front loading. The T allele was found in 73% of patients. Clopidogrel reduced adenosine diphosphate-induced platelet aggregation (P < 0.01), which was similar in carriers and non-carriers of the T allele throughout the study (P = 0.73). Clopidogrel reduced collagen-induced platelet aggregation only in non-carriers of the T allele (P = 0.03), which resulted in an increase in T allele carriers during the overall study (P = 0.04). In conclusion, the T allele of the GP Ia gene modulates platelet aggregation and clopidogrel antiplatelet effects, suggesting an enhanced reactivity to fibrillar collagens (exposed during coronary stenting) in T allele carriers and might contribute to an increased thrombotic risk in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Aged
  • Clopidogrel
  • Collagen / metabolism
  • Coronary Disease / surgery
  • Female
  • Humans
  • Integrin alpha2 / genetics*
  • Integrin alpha2 / metabolism
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Polymorphism, Genetic*
  • Stents / adverse effects
  • Thrombosis / genetics*
  • Thrombosis / metabolism
  • Thrombosis / prevention & control*
  • Ticlopidine / administration & dosage*
  • Ticlopidine / analogs & derivatives*

Substances

  • Integrin alpha2
  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Collagen
  • Clopidogrel
  • Ticlopidine