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Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin dose in Gaza-Palestine

Basim Mohammad Ayesh1,1, Ahmed Shaker Abu Shaaban2,2, Abdalla Asaf Abed3,3

  • 1Department of Laboratory Medical Sciences, Faculty of Applied Sciences, Alaqsa University, Gaza, Palestine.

Future Science OA
|March 24, 2018
PubMed

Insights

The international warfarin pharmacogenetics consortium algorithm accurately predicts stable warfarin dose in Palestinian patients. This pharmacogenetic approach offers a reliable method for personalized warfarin dosing in this population.

Area of Science:

  • Pharmacogenetics
  • Clinical Pharmacology
  • Genomics

Background:

  • Warfarin dosing requires careful management due to its narrow therapeutic index.
  • Genetic variations in CYP2C9 and VKORC1 significantly influence warfarin metabolism and response.
  • Predictive algorithms aim to optimize warfarin dosage for individual patients.

Purpose of the Study:

  • To assess the applicability of a warfarin pharmacogenetics algorithm for predicting stable warfarin dose (WSD) in Palestinian patients.
  • To compare the performance of the international warfarin pharmacogenetics consortium algorithm against clinical and fixed-dose algorithms.

Main Methods:

  • Retrospective calculation of warfarin doses for 101 Palestinian patients using three distinct models.
  • Evaluation of algorithm performance in a subset of 47 patients who had achieved a stable warfarin dose.
  • Analysis included CYP2C9*2, *3, and VKORC1-1639G>A allele frequencies.

Main Results:

  • The frequency of CYP2C9*2, *3, and VKORC1-1639G>A alleles in the study population was 13.6%, 0.0%, and 46.5%, respectively.
  • The international warfarin pharmacogenetics consortium algorithm demonstrated superior reliability with a Mean Absolute Error (MAE) of 8.9 ± 1.4 and R² of 0.350.
  • Both the clinical algorithm (MAE = 10.4 ± 1.4; R² = 0.128) and the fixed-dose algorithm (MAE = 11.1 ± 1.7) showed lower reliability.

Conclusions:

  • The international warfarin pharmacogenetics consortium algorithm is a reliable tool for predicting stable warfarin dose in the Palestinian population.
  • Pharmacogenetic-guided dosing can improve warfarin therapy management in this demographic.
  • Further validation in larger cohorts is recommended to solidify these findings.
Abstract

Keywords:
CYP2C9Gaza stripIWPC algorithmVKORC1allelic frequencypharmacogeneticsvitamin K antagonistwarfarin

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