Frequency of CYP3A4, CYP3A5, CYP2C9, and CYP2C19 Variant Alleles in Patients Receiving Clopidogrel That Experience Repeat Acute Coronary Syndrome

Heart Vessels. 2009 Mar;24(2):73-8. doi: 10.1007/s00380-008-1085-2. Epub 2009 Apr 1.

Abstract

The presence of cytochrome P450 (CYP) variant alleles may reduce the activation of the prodrug clopidogrel to its active state. This research evaluated the frequency of variant alleles in the genes coding for CYP3A4, CYP3A5, CYP2C9, and CYP2C19 enzymes in patients on clopidogrel therapy and experiencing repeat acute coronary syndrome (ACS) compared to a control group with a matching ethnic composition. Real-time polymerase chain reaction was used for allelic discrimination. Complete data were obtained for 92 patients enrolled over a 3-month period. There were no significant differences in the presence of the examined CYP3A4, CYP3A5, CYP2C9, or CYP2C19 variant alleles between the two groups. The present data indicate that patients currently receiving clopidogrel therapy who present with repeat ACS do not have higher frequency of the examined variant alleles compared to a control group.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / enzymology
  • Acute Coronary Syndrome / genetics
  • Aged
  • Aged, 80 and over
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Drug Resistance / genetics
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Platelet Aggregation Inhibitors / metabolism
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prospective Studies
  • Recurrence
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / metabolism
  • Ticlopidine / therapeutic use
  • Treatment Failure

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Ticlopidine