Frequency of vitamin K oxidoreductase complex subunit-1 (VKORC1) polymorphisms and warfarin dose management in patients with venous thromboembolism

Pharmacogenomics J. 2018 Sep;18(5):646-651. doi: 10.1038/s41397-018-0037-1. Epub 2018 Aug 10.

Abstract

Warfarin works by inhibiting VKORC1, so polymorphisms of this gene modify the required drug dose. The aim of this study is to examine the relation between therapeutic weekly dose of warfarin and C1173T/G1639A polymorphism of VKORC1 in patients with VTE. Seventy-five patients with VTE were enrolled. Weekly warfarin doses and time (day) to reach therapeutic INR were evaluated retrospectively along with VKORC1-C1173T and G1639A alleles. The mean weekly warfarin dose was lower and time to reach therapeutic INR was shorter in homozygote alleles (AA and TT) (p < 0.05). The multivariate regression model was produced, R2 = 0.05% for age (p = 0.04), R2 = 6% for VKORC1 (p = 0.03), the model for estimating warfarin dose R2 = 17% (p > 0.05). In particular, patients who need overdose of warfarin or whose bleeding score is high, study of these polymorphisms can be considered.

MeSH terms

  • Aged
  • Alleles
  • Female
  • Genotype
  • Hemorrhage / drug therapy
  • Hemorrhage / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Retrospective Studies
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / genetics*
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / therapeutic use*

Substances

  • Warfarin
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases