Effect of VKORC1, CYP2C9 and CYP4F2 genetic variants in early outcomes during acenocoumarol treatment

Pharmacogenomics. 2014 May;15(7):987-96. doi: 10.2217/pgs.13.232.

Abstract

Aim: To analyze VKORC1, CYP2C9 and CYP4F2 polymorphisms in relation to the main outcomes in the first stages of acenocoumarol therapy.

Patients & methods: Nine hundred and forty one patients who had started therapy and in whom time to stable dosage, time to over-anticoagulation and adverse events occurred during 3 first months were retrospectively analyzed.

Results: VKORC1 AA patients needed fewer days to reach stable dosage (p = 0.017). International normalized ratio [INR] at 72 h, and VKORC1 and CYP2C9 genotypes conditioned INR values >2.5 (p < 0.001, p = 0.002 and p < 0.001, respectively), whereas CYP4F2 T carriers had a low risk of the same outcome (p = 0.009). In regards to combined genotypes, CYP4F2 had a significant effect on over-anticoagulation at the beginning of therapy except for the VKORC1 AA and CYP2C9*3 combination.

Conclusion: In addition to VKORC1 and CYP2C9, CYP4F2 gene has a slight but significant role in reaching INR >2.5 during the first weeks of acenocoumarol therapy.

Keywords: CYP2C9; CYP4F2; VKORC1; acenocoumarol; outcomes; pharmacogenetics; polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acenocoumarol / administration & dosage*
  • Acenocoumarol / adverse effects
  • Adult
  • Aged
  • Biomarkers, Pharmacological
  • Blood Coagulation Disorders / drug therapy*
  • Blood Coagulation Disorders / genetics
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P450 Family 4
  • Female
  • Genotype
  • Humans
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Treatment Outcome
  • Vitamin K Epoxide Reductases / genetics*

Substances

  • Biomarkers, Pharmacological
  • Cytochrome P-450 Enzyme System
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Cytochrome P450 Family 4
  • CYP4F2 protein, human
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
  • Acenocoumarol