Warfarin pharmacogenetics in a black Zimbabwean cohort: an observational prospective study

Pharmacogenomics. 2023 Jul;24(10):529-538. doi: 10.2217/pgs-2023-0089. Epub 2023 Jul 12.

Abstract

Aim: A prospective observational study was conducted to evaluate the feasibility of implementing clinical guidelines for warfarin dosing in black Zimbabwean patients. Methods: CYP2C9*5, CYP2C9*6, CYP2C9*8 and CYP2C9*11 and VKORC1 c. 1639 G>A variations were observed in 62 study patients. Results & Conclusion: Overall, 39/62 (62.90%) participants did not receive a warfarin starting dose as would have been recommended by Clinical Pharmacogenetics Implementation Consortium guidelines. US FDA and Dutch Pharmacogenetics Working Group guidelines are based on CYP2C9*2 and CYP2C9*3 only, hence, unlikely useful in this cohort, where such variants were not detected. Clinical Pharmacogenetics Implementation Consortium guidelines, on the other hand, have a specific recommendation on the African-specific variants CYP2C9*5, CYP2C9*6 and CYP2C9*11, and are hence suitable for implementation in Zimbabwe and would help optimize warfarin doses in patients in the study cohort.

Keywords: CYP2C9; VKORC1; genetic variation; pharmacogenomics; warfarin.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / therapeutic use
  • Aryl Hydrocarbon Hydroxylases* / genetics
  • Cytochrome P-450 CYP2C9 / genetics
  • Genotype
  • Humans
  • Pharmacogenetics / methods
  • Prospective Studies
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin* / therapeutic use
  • Zimbabwe

Substances

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