Coexisting Polymorphisms of P2Y12 and CYP2C19 Genes as a Risk Factor for Persistent Platelet Activation With Clopidogrel

Circ J. 2008 Jul;72(7):1165-9. doi: 10.1253/circj.72.1165.

Abstract

Background: Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation.

Methods and results: In 105 patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention, platelet function was measured and registered as closure time in the test with collagen and adenosine diphosphate (CADP-CT). Patients were followed for 12 months for death or recurrent myocardial infarction (MI). Genotyping revealed 7 carriers of both the C allele of P2Y12 and A allele of CYP2C19 (group 1), 14 carriers of the T allele of P2Y12 and A allele of CYP2C19 (group 2), 17 carriers of the C allele of P2Y12 and G allele of CYP2C19 (group 3) and 67 carriers of the T allele of P2Y12 and G allele of CYP2C19 (controls). The median CADP-CT value was significantly lower in group 1 than in group 2 or 3 (p<0.01) or controls (p<0.002), but did not differ between group 2 or 3 and controls. There were 2 cardiovascular deaths and 4 MI during follow-up, and the median CADP-CT value was lower in these patients (p=0.09).

Conclusions: Coexisting, rather then single, polymorphisms of different genes may be related to persistent platelet activation while on clopidogrel, which raises concern about harm in patients with ACS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / epidemiology
  • Acute Coronary Syndrome / genetics*
  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Drug Resistance / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Activation / drug effects
  • Platelet Activation / genetics
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic
  • Receptors, Purinergic P2 / genetics*
  • Receptors, Purinergic P2Y12
  • Risk Factors
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine