THE USE OF GENETIC TESTING FOR PERSONALIZED OPTIMIZATION OF WARFARIN THERAPY
The aim of our study was to investigate the frequency of occurrence of CYP2C9 *2, *3 (R144S and I359L), C+1173T VKORC and G > A rs2108622 (V433M) CYP 4F2 and C > G rs11676382 GGCX genes polymorphisms in patients of the West Siberian region of Russia, as well as to assess the contribution of these genetic markers to the change of therapeutic dosage of warfarin for this group of patients. The study included 118 patients (mean age 51 12 years) from the West Siberian region taking warfarin more than 1 year. Effectiveness of warfarin was assessed by the International Normalized Ratio. Presence of alleles was determined by polymerase chain reaction. Significant differences of average daily dose of warfarin depending on the VKORC genotype were revealed: for patients with genotype CC average dose was 7,1 ± 2,3 mg, with genotype CT - 4,8 ± 1,9, with genotype TT - 2,8 ± 0,6 mg. There were not significant differences in selected doses of warfarin depending on the CYP2C9 *2 genotypes. Patients with «slow allele» CYP2C9*3 required a lower dose of warfarin (*1/*1 - 5,8 ± 2,5 and *1/*3 - 4,1 ± 2,6 mg. Presence of CYP2C9 *2 or *3 alleles resulted in tendency to decrease of average daily dose of warfarin based on VCORK1 genotype. Thus, genotype VKORC1 and CYP2C9*3 among other genetic markers contributes most to the titration of a therapeutic dosage of warfarin in the West Siberian population.