Pharmacogenetics of warfarin: challenges and opportunities

J Hum Genet. 2013 Jun;58(6):334-8. doi: 10.1038/jhg.2013.40. Epub 2013 May 9.

Abstract

Since the introduction in the 1950s, warfarin has become the commonly used oral anticoagulant for the prevention of thromboembolism in patients with deep vein thrombosis, atrial fibrillation or prosthetic heart valve replacement. Warfarin is highly efficacious; however, achieving the desired anticoagulation is difficult because of its narrow therapeutic window and highly variable dose response among individuals. Bleeding is often associated with overdose of warfarin. There is overwhelming evidence that an individual's warfarin maintenance is associated with clinical factors and genetic variations, most notably polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase subunit 1. Numerous dose-prediction algorithms incorporating both genetic and clinical factors have been developed and tested clinically. However, results from major clinical trials are not available yet. This review aims to provide an overview of the field of warfarin which includes information about the drug, genetics of warfarin dose requirements, dosing algorithms developed and the challenges for the clinical implementation of warfarin pharmacogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Administration, Oral
  • Algorithms
  • Anticoagulants / administration & dosage*
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / prevention & control
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Humans
  • Pharmacogenetics*
  • Polymorphism, Genetic
  • Randomized Controlled Trials as Topic
  • Thromboembolism / drug therapy
  • Thromboembolism / prevention & control
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / administration & dosage*

Substances

  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Vitamin K Epoxide Reductases