Impact of cytochrome P450 2C9 polymorphism on warfarin therapy in saudi population

Abstract

Background and Objective: Individualization of therapy based on patient’s genetic profile is particularly important with certain drugs. Warfarin is one of vitamin K antagonists (VKA) that is widely used anticoagulant with inter and intra-individual dosage variability depending on many non-genetic and genetic factors. This study aimed to evaluate the effect of cytochrome P450 2C9 isoform (CYP2C9) polymorphism on the dosage variability and therapeutic efficacy of warfarin in a subset of Saudi patient. Materials and Methods: The study included 112 patients on regular warfarin therapy for various causes. Genomic DNA of all patients was isolated and quantified. The DNA samples were genotyped for CYP2C9*2 and CYP2C9*3 alleles by TaqMan allelic discrimination genotyping method. The primary outcome was time in therapeutic range (TTR). Data were compared utilizing one-way ANOVA, independent measures t-tests and the corresponding non-parametric test and Fisher’s exact test. Results: The dose of warfarin was less for patient expressing either genotype variant alleles of CYP2C9. Time in therapeutic range was not significantly different utilizing one-way ANOVA test when evaluating CYP2C9 genotype. Patients homozygous for *2 allele had less TTR (50.0%, p = 0.10) and lower average weekly dose than the others. Conclusion: CYP2C9 polymorphism influences warfarin dosage and efficacy among a subset of Saudi population and tends to be a good clinical practice particularly in patients experiencing excessive bleeding or patients with less TTR.