Role of Genetic Variations in the CYP2C9 Gene in Determining the Optimal Dose of Warfarin in a Group of Syrian Patients

Abstract

Genetic variations in drug metabolizing hepatic CYP2C9 gene determine the optimal dose for many drugs including anticoagulants such as warfarin.  Here we sought to detect the frequency distribution of genetic variations of CYP2C9 gene and to determine its potential role in the control of warfarin dose in Syrian patients. The study included 125 patients with high risk of thrombosis of adults who visited the Heart Disease & Surgery Hospital (HDSH) and Aleppo University Hospital (AUH) and treated with warfarin as oral anticoagulant therapy, and the dose-corrected by the international normalized ratio (INR) at least three months ago. Genomic DNA was extracted from blood samples, and genotype analysis for CYP2C9*2 and  CYP2C9*3 variant alleles was done by polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). Data were analyzed using SPSS version 20. The results obtained in this study suggest that Genotype frequency distribution of CYP2C9*2 and CYP2C9*3 variant alleles was found to be different from other populations and has significant effect on warfarin dose requirement (p<0.05). It is concluded that there is a need to include CYP2C9 genetic variations detection tests in the warfarin dosing algorithm, as this has an important role in reducing serious hemorrhagic complications, especially in patients with the CYP2C9*2/*2 and CYP2C9*3/*3 homozygous mutant genotypes.