Feasibility of a microarray-based point-of-care CYP2C19 genotyping test for predicting clopidogrel on-treatment platelet reactivity

Biomed Res Int. 2013:2013:154073. doi: 10.1155/2013/154073. Epub 2013 Mar 28.

Abstract

Clopidogrel is a prodrug which is converted into active metabolite by cytochrome P450 isoenzyme, CYP2C19. Numerous polymorphisms of CYP2C19 are reported, and a strong link exists between loss-of-function (LOF) or gain-of-function polymorphisms, clopidogrel metabolism, and clinical outcome. Hence, a fully automated point-of-care CYP2C19 genotyping assay is more likely to bring personalized antiplatelet therapy into real practice. We assessed the feasibility of the Verigene 2C19/CBS Nucleic Acid Test, a fully automated microarray-based assay, compared to bidirectional sequencing, and performed VerifyNow P2Y12 assay to evaluate the effect of CYP2C19 polymorphisms on on-treatment platelet reactivity in 57 Korean patients treated with clopidogrel after percutaneous coronary intervention. The Verigene 2C19/CBS assay identified ∗2, ∗3, and ∗17 polymorphisms with 100% concordance to bidirectional sequencing in 180 minutes with little hands-on time. Patients were classified into 4 groups: extensive (∗1/∗1; n = 12, 21.1%), intermediate (∗1/∗2, ∗1/∗3; n = 33, 57.9%), poor (∗2/∗2, ∗2/∗3, and ∗3/∗3; n = 11, 19.3%), and ultrarapid metabolizers (∗1/∗17; n = 1, 1.8%). The prevalence of the CYP2C19 ∗2, ∗3, and ∗17 alleles was 36.0%, 12.3%, and 0.9%. Platelet reactivity showed gene dose response according to the number of CYP2C19 LOF allele. In conclusion, the Verigene 2C19/CBS assay gave accurate CYP2C19 genotype results which were in well match with the differing on-treatment platelet reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Blood Platelets / drug effects
  • Blood Platelets / pathology*
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Female
  • Genotype*
  • Humans
  • Male
  • Microarray Analysis
  • Platelet Count
  • Point-of-Care Systems
  • Polymorphism, Genetic
  • Precision Medicine
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*

Substances

  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine