Warfarin maintenance dose associated with genetic polymorphisms of CYP2C9

Background: Cytochrome P450 2C9 (CYP2C9) gene polymorphisms alters the required warfarin dose in patients, due to pharmacogenetic events. This study aimed to identify the frequency of the allele CYP2C9 polymorphic variants *2 and *3, and the association of these allelic variants with warfarin dosage in the population of the west Azerbaijan province in Iran. Methods: one hundred and seventy patients receiving warfarin were examined to evaluate the genotype frequency of common CYP2C9 polymorphisms. Genotype analysis for CYP2C9*2 and CYP2C9*3 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. To assess if the dosage is different between genotypes we used one-way analysis of variance (ANOVA). Results: Frequency of the two variants in studied subjects was 12 % for CYP2C9*2 and 25.8 % for CYP2C9*3. Comparison of the warfarin daily maintenance dose between genotype groups showed that the daily mean dose of warfarin in patients who have homozygous wild-type genotype for CYP2C9 (*1/*1) was 5.26 +/- 2.32 mg, which was significantly higher compared to *1/*2, *1/*3 (3.57 +/- 2.25 mg, p <0.001) and *2/*2, *2/*3 and *3/*3 patients (3.76 +/- 2.4 mg, p =0.024). Further analysis revealed that the allelic frequency of CYP2C9 polymorphisms in the study population was similar to that of the Turkish population. Conclusions: Due to the relatively high frequency of CYP2C9 polymorphisms in the study population, the clinicians should become aware of these results to reduce the risk of hemorrhage when prescribing warfarin.