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[Companion Diagnostics for Thrombotic Disease]

Yuya Masuda, Kazuhiko Matsuno, Chikara Shimizu

    Rinsho Byori. the Japanese Journal of Clinical Pathology
    |March 22, 2016
    PubMed

    Insights

    Pharmacogenomic (PGx) studies reveal genetic factors influencing warfarin dosing. Novel oral anticoagulants (NOACs) offer alternatives, but PGx may also impact their efficacy and safety for personalized anticoagulant therapy.

    Area of Science:

    • Pharmacogenomics
    • Cardiovascular Medicine
    • Drug Metabolism

    Background:

    • Increasing incidence of thrombotic diseases like myocardial infarction and ischemic stroke in Japan.
    • Warfarin, a long-standing oral anticoagulant, presents challenges in dosing due to inter-individual variability and a narrow therapeutic range.
    • Genetic variations in CYP2C9 and VKORC1 significantly influence warfarin sensitivity.

    Purpose of the Study:

    • To review the role of pharmacogenomics (PGx) in personalized warfarin therapy.
    • To discuss the emergence and potential PGx implications of novel oral anticoagulants (NOACs).
    • To highlight the need for further research in personalized anticoagulant strategies.

    Main Methods:

    • Review of recent pharmacogenomic studies on warfarin.
    • Analysis of genetic polymorphisms affecting drug metabolism and target enzymes (CYP2C9, VKORC1).
    • Examination of clinical data and research on NOACs (dabigatran, rivaroxaban, apixaban, edoxaban).

    Main Results:

    • Specific single nucleotide polymorphisms (SNPs) in CYP2C9 and VKORC1 explain a significant portion of warfarin dose variability.
    • PGx-based algorithms are being developed for personalized warfarin dosing.
    • While NOACs are fixed-dose, inter-individual variability in drug concentration, potentially due to gene polymorphisms (e.g., dabigatran), has been observed.

    Conclusions:

    • Pharmacogenomics is crucial for optimizing warfarin therapy and enabling personalized treatment.
    • Further investigation into the pharmacogenomic aspects of NOACs is necessary for safer and more effective anticoagulant therapy.
    • Advancements in PGx are expected to drive personalized anticoagulant strategies in the future.

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