Genetic variation of VKORC1 and CYP4F2 genes related to warfarin maintenance dose in patients with myocardial infarction

J Biomed Biotechnol. 2011:2011:739751. doi: 10.1155/2011/739751. Epub 2010 Nov 24.

Abstract

The aim of this study was to investigate whether the VKORC1*3 (rs7294/9041 G > A), VKORC1*4 (rs17708472/6009 C > T), and CYP4F2 (rs2108622/1347 C > T) polymorphisms were associated with elevated warfarin maintenance dose requirements in patients with myocardial infarction (n = 105) from the Warfarin Aspirin Reinfarction Study (WARIS-II). We found significant associations between elevated warfarin dose requirements and VKORC1*3 and VKORC1*4 polymorphisms (P = .001 and P = .004, resp.), whereas CYP4F2 (1347 C > T) showed a weak association on higher warfarin dose requirements (P = .09). However, analysing these variant alleles in a regression analysis together with our previously reported data on VKORC1*2, CYP2C9*2 and CYP2C9*3 polymorphisms, gave no significant associations for neither VKORC1*3, VKORC1*4 nor CYP4F2 (1347 C > T). In conclusion, in patients with myocardial infarction, the individual contribution to warfarin dose requirements from VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms was negligible. Our results indicate that pharmacogenetic testing for VKORC1*2, CYP2C9*2 and CYP2C9*3 is more informative regarding warfarin dose requirements than testing for VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P450 Family 4
  • Dose-Response Relationship, Drug
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / genetics*
  • Polymorphism, Single Nucleotide
  • Regression Analysis
  • Statistics, Nonparametric
  • Vitamin K Epoxide Reductases
  • Warfarin / administration & dosage*

Substances

  • Warfarin
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P450 Family 4
  • CYP4F2 protein, human
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases