The GPIIIa PlA polymorphism and the platelet hyperactivity in Tunisian patients with stable coronary artery disease treated with aspirin

Thromb Res. 2010 Jun;125(6):e265-8. doi: 10.1016/j.thromres.2010.01.011.

Abstract

Background: Various genetic polymorphisms have been proposed to explain the persistent platelet hyperactivity (HPR) under aspirin treatment. PlA polymorphism of platelet GPIIIa receptor has been largely studied. However, its influence on platelet sensitivity to aspirin remains controversial.

Objectives: The aim of this prospective study is to investigate whether this PlA polymorphism is associated with a greater prevalence of HPR in stable coronary artery disease patients Material and Methods: 188 stable coronary artery disease patients were included. Platelet aspirin inhibitory effect was determined with PFA-100 using Collagen/Epinephrine closure time (CEPI-CT). A CEPI-CT<160sec was defining the HPR status. GPIIIa PlA polymorphism was established using polymerase chain reaction and classical restriction fragments length polymorphism.

Results: The observed frequencies of different genotypes were not different from those predicted by the Hardy-Weinberg equilibrium: PlA1/lA1 (55.3%), PlA1/PlA2 (39.4%) and PlA2/PlA2 (5.3%). HPR patients with inadequate aspirin inhibition were significantly more often homozygous PlA1/A1 (65.4% vs. 47.7%, p=0.015). After multivariate analysis, PlA1/A1 genotype was the only independent risk factor for persistent HPR (OR: 2.07; 95% CI [1.14 to 3.76; p=0.016).

Conclusion: In CAD patients receiving daily low dose of aspirin, there is a significant and independent association between the expression of GPIIIa PlA1 allele and the occurrence of persistent HPR detected with PFA-100.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / pharmacology
  • Aspirin / therapeutic use*
  • Blood Platelets / drug effects*
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / genetics
  • Female
  • Genotype
  • Humans
  • Integrin beta3 / genetics*
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors
  • Platelet Function Tests
  • Polymorphism, Genetic*
  • Tunisia / epidemiology

Substances

  • Integrin beta3
  • Platelet Aggregation Inhibitors
  • Aspirin