Warfarin pharmacogenomics: recommendations with available patented clinical technologies

Recent Pat Biotechnol. 2014;8(2):110-5. doi: 10.2174/1872208309666140904112003.

Abstract

Warfarin pharmacogenomic testing has become a prime example of the utility of personalized molecular testing in the modern clinical laboratory. Warfarin is a commonly used drug for the prevention and treatment of thromboembolic complications in a variety of clinical situations. However, a number of factors lead to a high interindividual variability in dose requirements. Among the primary factors in this variability are genetic polymorphisms in general patient populations, which can account for 35-50% of varying dose requirements among patients. In this review, we discuss the implications of polymorphisms in the cytochrome P-450 enzyme 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Enzyme Complex subunit 1 (VKORC1) as they relate to therapeutic warfarin dosing. We discuss the clinical utility of pharmacogenomics testing as related to warfarin dosing, and propose a clinical model for the implementation of the pharmacogenomic test results. Finally, we provide a brief overview of the currently available commercial testing platforms with discussion of the complexities of utilizing patented methodologies in bringing genetic testing such as this to the clinical laboratory.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Anticoagulants / metabolism
  • Anticoagulants / therapeutic use*
  • Cytochrome P-450 CYP2C9 / genetics
  • Cytochrome P-450 CYP2C9 / metabolism
  • Genotyping Techniques
  • Hemorrhage / etiology
  • Humans
  • Patents as Topic
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide
  • Thromboembolism / drug therapy
  • Thromboembolism / genetics
  • Thromboembolism / pathology
  • Vitamin K Epoxide Reductases / genetics
  • Vitamin K Epoxide Reductases / metabolism
  • Warfarin / metabolism
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Warfarin
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases