The population attributable fraction as a measure of the impact of warfarin pharmacogenetic testing

Pharmacogenomics. 2012 Aug;13(11):1247-56. doi: 10.2217/pgs.12.104.

Abstract

Aim: We aimed to estimate the population impact of warfarin pharmacogenetic testing (WPGT) across multiple populations.

Materials & methods: We used the expanded International Warfarin Pharmacogenetics Consortium data set and genotype frequencies from HapMap to simulate dose distributions for each CYP2C9/VKORC1 genotype combination in the different races, and calculated the population attributable fraction as a measure of population impact of WPGT. WPGT was compared to both clinical and fixed-dose algorithms to estimate the benefits of WPGT.

Results: Our dose simulation revealed different dose requirements in difference races and considerable overlap in dose distributions of different genotype combinations. Population attributable fraction calculations suggest that complete implementation of WPGT can reduce inaccurate dosing by 18-24% in white individuals. However black, Japanese and Chinese patients do not benefit from WPGT, especially when compared against a race-specific fixed dose.

Conclusion: Our findings support WPGT in white individuals but not in black, Japanese and Chinese individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / administration & dosage
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian People / genetics
  • Black People / genetics
  • Black or African American / genetics
  • Blood Coagulation / drug effects
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Genetics, Population
  • Genotype*
  • HapMap Project
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Pharmacogenetics
  • Vitamin K Epoxide Reductases
  • Warfarin / administration & dosage*
  • White People / genetics

Substances

  • Anticoagulants
  • Warfarin
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases