Interpretation of the effect of CYP2C9, VKORC1 and CYP4F2 variants on warfarin dosing adjustment in Turkey

Mol Biol Rep. 2019 Apr;46(2):1825-1833. doi: 10.1007/s11033-019-04634-9. Epub 2019 Feb 2.


It was aimed to underline the importance and explain the meaning of genetic testing in warfarin dosing and investigate and evaluate the contributions of the CYP2C9, VKORC1, and CYP4F2 variants in a Turkish population. Two hundred patients were genotyped for CYP2C9 (rs1799853, rs1057910 and rs56165452), VKORC1 (rs9934438, rs8050894, rs9923231, rs7294 and rs2359612) and CYP4F2 (rs2108622), yet, only 127 patients were found suitable for further evaluation in terms of their personal response to warfarin due to long term usage and available INR and dose usage information. The DNA sequences were determined by the ABI PRISM 3100 Genetic Analyzer to 3130xl System (Applied Biosystems, Foster City, California). Warfarin dose application suggestions by, FDA and MayoClinic were followed. Dose requirements in the Turkish population were found higher than the suggested doses by The multivariate logistic regression analysis reveals the utilization of VCORC1 genetic evaluation is valuable in warfarin dosing (low and moderate vs. high) in this study (p < 0.001). The present study provides findings for clinicians to adapt the genetic data to the daily practice. We observed that the VKORC1 variant showed a more potent impact in warfarin dosing in this study.

Keywords: Drug sensitivity; Pharmacogenetics; Warfarin dosing.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Pharmacological
  • Cytochrome P-450 CYP2C9 / genetics
  • Cytochrome P-450 CYP2C9 / metabolism*
  • Cytochrome P450 Family 4 / genetics
  • Cytochrome P450 Family 4 / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Frequency
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Turkey
  • Vitamin K Epoxide Reductases / genetics
  • Vitamin K Epoxide Reductases / metabolism*
  • Warfarin / administration & dosage
  • Warfarin / pharmacology*


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