Polymorphic variants in acenocoumarol-related genes CYP2C9 and VKORC1 and their frequencies in Bulgarian population
DOI:
https://doi.org/10.2478/AMB-2025-0057Keywords:
CYP2C9, VKORC1, acenocoumarol, frequencies, BulgariansAbstract
Introduction. Acenocoumarol is an indirect anticoagulant, a 4-hydroxycoumarin derivative, which is used in the treatment of various thromboembolic diseases. Polymorphic variants in the CYP2C9 and VKORC1 genes significantly contribute to the optimal maintenance acenocoumarol dose requirements in different populations. Purpose. The purpose of the study was to establish the allele and genotype frequencies of the following polymorphic variants: CYP2C9*2; CYP2C9*3; VKORC1*2A; VKORC1*2B; VKORC1*3 and VKORC1*4 in Bulgarian participants and to compare them to these in other European populations. Materials and Methods. Our study included 155 unrelated controls from different regions of Bulgaria. Genomic DNAs were extracted from peripheral venous blood. The analysis of selected polymorphisms was performed by High Resolution Melting Analysis. The allele frequencies of various genotypes were calculated by Hardy–Weinberg Equilibrium (HWE). Results. The obtained frequencies of polymorphisms studied in this study are presented below: 1. CYP2C9*2 – CC (85.71%), CT (13.47%), TT (0.82%), C (92.00%), T (8.00%), HWE χ²=2.58, 2. CYP2C9*3 – CC (0.04%), CT (16.94%), TT (82.66%), C (8.87%), T (91.13%), HWE χ²=0.26, 3. VKORC1*2A – GG (32.47%), GA (48.70%), AA (18.83%), G (56.82%), A (43.18%), HWE χ²=0.01, 4. VKORC1*2A – GG (32.47%), GA (48.70%), AA (18.83%), G (56.82%), A (43.18%), HWE χ²=0.01, 5. VKORC1*2B – GG (11.43%), GT (44.29%), TT (44.29%), G (33.57%), T (66.43%), HWE χ²=0.01, 6. VKORC1*3 – GG (41.04%), GA (48.23%), AA (9.93%), G (65.96%), A (34.04%), HWE χ²=0.77, 7. VKORC1*4 – CC (64.93%), CT (32.09%), TT (2.99%), C (80.97%), T (19.03%), HWE χ²=1.51. Conclusion. The established genotypic and allelic frequencies of the studied polymorphisms in CYP2C9 and VKORC1 were according to the Hardy–Weinberg equilibrium and correspond to these in other European populations.
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Copyright (c) 2025 R. Tzveova, A. Dimitrova-Karamfilova, S. Vandeva, P. Atanasov, D. Pendicheva-Duhlenska, G. Nachev, V. Mitev, R. Kaneva (Author)
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Journal Acta Medica Bulgarica 
