Warfarin maintenance dose associated with genetic polymorphisms of CYP2C9

Abstract

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.

Keywords: CYP2C9 polymorphisms; PCR-RFLP; pharmacogenetic; polymerase chain reaction-restriction fragment length polymorphism assay; warfarin.

Figure 1. AvaII digestion products. Lane M, 100-bp ladder; lanes 1 and 9 two CT heterozygotes with fragments of 420-bp, 363-bp; lane 5, mutant homozygote AA with fragment of 420-bp; and lanes 2, 3, 4, 6, 7, and 8, wild homozygote CC with fragment of 363-bp.

Figure 2. NsiI digestion products. Lane M, 100-bp ladder; lanes 1 and 6 two CA heterozygotes with fragments of 131-bp and 110-bp; lane 3, mutant homozygote CC with fragment of 131-bp; lanes 2, 4, and 5, wild homozygote with fragment of 110-bp.

Figure 3. Boxplot showing the different genotype groups of CYP2C9 against the daily warfarin dosage. Boxes indicate the median and interquartile ranges. Vertical lines above and below boxes indicate the minimum and maximum values. The numbers above whiskers show mean values. An asterisk shows each outlier.