Frequencies of polymorphisms in genes affecting the pharmacokinetics of warfarin in the Zaporizhzhia region

Abstract

The aim of the study: to establish the frequencies of polymorphisms in VKORC1, CYP2C9 and CYP4F2 genes among residents of the Zaporizhzhia region. Materials and methods. A total of 150 persons (62 male, 88 female) with a median age of 46 years (26; 58) undergoing preventive examination at the Medical Educational and Scientific Center "University Clinic" of Zaporizhzhia State Medical University (ZSMU). The CYP2C9, CYP4F2, VKORC1 genes polymorphisms in atrial fibrillation patients were determined in the Department of Molecular Genetic Studies of the ZSMU Medical Laboratory Center. Amplification of DNA fragments containing polymorphic regions was performed using multiplex real time polymerase chain reaction with Warfarin Pharmacogenetics kits (LLC NPO DNA Technology) in a CFX-96 thermocycler (BioRad) with a fluorescence detection scheme. Results. It was determined that among Zaporizhzhia region residents, the frequencies of CYP2C9*2 genotypes were: C/C 77.3 %, C/T - 22.7 %, T/T - 0; CYP2C9*3 genotypes: A/A - 88.7 %, A/C - 10.7 %, C/C - 0.6 %; CYP4F2 genotypes: C/C - 56.0 %, C/T - 35.3 %, T/T - 8.7 %; VKORC1 genotypes: G/G - 38.0 %, G/A - 50.0 %, A/A - 12.0 %. There were no statistically significant differences in the distribution of genotype frequencies between males and females and between different age groups. The frequencies of CYP2C9, CYP4F2, VKORC1 genotypes in different populations were compared. Their variability in different geographic regions was established. Conclusions. CYP4F2 and VKORC1 genes polymorphisms are more common in the Zaporizhzhia region, while the prevalence of CYP2C9*2 and CYP2C9*3 genes polymorphisms is much lower. It is necessary to take into account the prevalence of genes polymorphisms that affect warfarin metabolism for each individual population to select its dose by pharmacogenetic testing.