Pharmacogenomic impact of CYP2C19 variation on clopidogrel therapy in precision cardiovascular medicine

Sherry Ann Brown, Naveen Pereira

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel. Individuals may be classified as poor, intermediate, extensive, or ultrarapid metabolizers, based on whether they carry wild type or polymorphic CYP2C19 alleles. Variant alleles differentially impact platelet reactivity, concentration of plasma clopidogrel metabolites, and clinical outcomes. Interestingly, response to clopidogrel appears to be modulated by additional factors, such as sociodemographic characteristics, risk factors for ischemic heart disease, and drug-drug interactions. Furthermore, systems medicine studies suggest that a broader approach may be required to adequately assess, predict, preempt, and manage variation in antiplatelet response. Transcriptomics, epigenomics, exposomics, miRNAomics, proteomics, metabolomics, microbiomics, and mathematical, computational, and molecular modeling should be integrated with pharmacogenomics for enhanced prediction and individualized care. In this review of pharmacogenomic variation of CYP450, a systems medicine approach is described for tailoring antiplatelet therapy in clinical practice of precision cardiovascular medicine.

Original languageEnglish (US)
Article number8
JournalJournal of Personalized Medicine
Volume8
Issue number1
DOIs
StatePublished - Mar 2018

Keywords

  • Antiplatelet therapy
  • CYP2C19
  • CYP450
  • Clopidogrel
  • Genetics variants
  • Pharmacogenomics
  • Precision cardiovascular medicine

ASJC Scopus subject areas

  • Medicine (miscellaneous)

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