The Effect of CYP2C9 and VKORC1 Genetic Polymorphism on Warfarin Dose Requirements in a Sample of Iraqi Patients

Abstract

Background: Warfarin is the most widely used oral anticoagulant for the prevention and treatment of thromboembolic disorders. Because of narrow therapeutic index and various genetic and non-genetic factors that influence the disposition of the drug, its dose undergoes a great variability. The aim of this study was to determine the allelic variants of CYP2C9 and VKORC1 genes in Iraqi patients, and to investigate the contribution of genetic on warfarin dose requirements.Methods: A cross sectional study was carried out on a sample of Iraqi patients from Baghdad city who were admitted to Ibn AL-Bitar Specialized Center for cardiac surgery. Blood samples of all patients were collected for both hematological and genetic analysis utilizing standard techniques.Results: The frequency of CYP2C9*3 allele was 9.4% whereas that of CYP2C9*2 allele was 13.7%. The frequency of (VKORC1-1639G) allele was 58.75% and the frequency of (VKORC1-1639A) allele was 41.25%. Patients’ daily warfarin doses were administered according to their genotype.Conclusion:It can be concluded that CYP2C9*3 and VKORC1 had significant effect on warfarin dose. New warfarin-dosing algorithm was developed based on CYP2C9*3 and VKORC1genotypes for predicting the required dose of warfarin.

Keywords

• warfarin dose
• warfarin pharmacogenetics
• warfarin pharmacogenomics
• cyp2c9
• vkorc1