The aim of this study was to investigate the impact of CYP2C9 polymorphism on dose warfarin and international normalized ratio (INR) values changes.
Materials and methods: The study included 155 patients after heart valve replacement (67.74% male, 32.26% women, average age 51.7±1.1 years). Patients received warfarin treatment from initial dose of 5 mg/day. Subgroup A (n=35) – patients with INR values out of therapeutic range and subgroup B (n=120) patients with INR values from 2.5 to 3.5. For determination of allelic variants *2 and *3 of CYP2C9 gene the method of allele-specific PCR has been used.
Results: Frequencies of the genotype CYP2C9*1/*1 (a “wild” type) was 66.45%. The frequencies of the heterozygous genotypes CYP2C9*1/*2, CYP2C9*1/*3, homozygous genotypes CYP2C9*2/*2, CYP2C9*3/*3 and compound heterozygous genotype CYP2C9*2/*3 were 18.06%, 11.61%, 0.65%, 0.65%, 2.58% respectively. The mean warfarin daily dose requirement was highest in patients with genotype CYP2C9*1/*1 (3.7±0.15 mg), compared to patients with genotypes CYP2C9*1/*3 (2.47±0.26 mg) and CYP2C9*2/*3 (0.78±0.16 mg) (P0.05), similar to patients with genotype CYP2C9*1/*2 (3.24±0.22 mg) (P0.05). Patients with genotype CYP2C9*1/*3 had higher risk of over-anticoagulation during warfarin therapy, compared to patients with wild-type genotype (P0.05).
Conclusions: This study showed that polymorphism of CYP2C9 affect warfarin dose requirements and INR values changes in patients after heart valve replacement.
Keywords: warfarin, dose, gene, genotype, INR.
Figure 1. Box plot of mean daily warfarin doses for different genotypes of CYP2C9.
