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. HIPPOKRATIA 2017, 21(2): 93-96.