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Differential Impact of Cytochrome 2C19 Allelic Variants on Three Different Platelet Function Tests in

Renske H Olie1,2,3, Rachelle R K Hensgens1,4, Petal A H M Wijnen4

  • 1Department of Internal Medicine, Maastricht University Medical Center+ (MUMC+), 6229 HX Maastricht, The Netherlands.

Journal of Clinical Medicine
|September 10, 2021
PubMed

Insights

The CYP2C19 genotype significantly impacts clopidogrel

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Chemistry

Background:

  • Platelet function tests (PFTs) assess clopidogrel efficacy.
  • Agreement between PFTs is limited.
  • CYP2C19 gene variants affect clopidogrel metabolism and platelet reactivity.

Purpose of the Study:

  • To investigate the differential impact of CYP2C19 genotype on three PFTs.
  • To understand variability in on-treatment platelet reactivity.

Main Methods:

  • Prospective cohort study of 308 patients post-percutaneous coronary intervention (PCI).
  • Simultaneous measurement of platelet reactivity using light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate assays.
  • CYP2C19 genotyping performed on whole blood.

Main Results:

  • CYP2C19 metabolizer status significantly affected LTA and VerifyNow results (p < 0.01).
  • Platelet reactivity increased with decreasing metabolizer status (poor > intermediate > extensive > rapid).
  • Multiplate assay showed no significant correlation with CYP2C19 metabolizer status (p = 0.10).

Conclusions:

  • CYP2C19 genotype correlates with on-treatment platelet reactivity for VerifyNow and LTA.
  • Multiplate results are less influenced by genetic factors, with patient-related variables prevailing.
  • Differential effects of CYP2C19 genotype contribute to PFT disagreement.

Keywords:
CYP2C19clopidogrelpharmacogeneticsplatelet activationplatelet function test

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