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The VKORC1 and CYP2C9 gene variants as pharmacogenetic factors in acenocoumarol therapy in Serbian patients - consideration of hypersensitivity and resistance

Authors :
Rakićević Ljiljana
Kovač Mirjana
Radojković Dragica
Radojković Milica
Source :
Srpski Arhiv za Celokupno Lekarstvo, Vol 150, Iss 3-4, Pp 156-162 (2022)
Publication Year :
2022
Publisher :
Serbian Medical Society, 2022.

Abstract

Introduction/Objective. Coumarin therapy represents one of the best models for applying pharmacogenetics. The contribution of factors influencing coumarin therapy can vary significantly between ethnic groups, which justifies conducting population-specific studies. The aim of this study was to analyze the influence of the most important genetic factors (VKORC1 and CYP2C9 genes) that affect coumarin therapy in patients from Serbia. Methods. A retrospective study involving 207 patients on acenocoumarol therapy was conducted. Genetic analyses were performed by direct sequencing. Influence on acenocoumarol dose of variants (VKORC1, CYP2C9*2, CYP2C9*3) causing hypersensitivity and VKORC1 variants causing resistance to acenocoumarol were analyzed. Multiple regression analysis was used to design a mathematical model for predicting individual drug dosage based on clinical-demographic and genetic data. Results. The study confirmed significant influence of the analyzed genetic factors on acenocoumarol maintenance dose. We designed mathematical model for predicting individual acenocoumarol dose and its unadjusted R2 was 61.8. In the testing cohort, our model gave R2 value of 42.6 and showed better prediction in comparison with model given by other authors. In the analyzed patients, nine different variants in the VKORC1 coding region were found. Among carriers of these variants 78% were completely resistant, and it was not possible to achieve therapeutic effect even with high doses of acenocoumarol. Conclusions. Population-specific model for prediction individual dose of acenocoumarol, may show advantages over protocols that are used in a generalized manner. Also, VKORC1 variants which cause coumarin resistance should be considered when planning therapy.

Details

Language :
English, Serbian
ISSN :
03708179 and 24060895
Volume :
150
Issue :
3-4
Database :
Directory of Open Access Journals
Journal :
Srpski Arhiv za Celokupno Lekarstvo
Publication Type :
Academic Journal
Accession number :
edsdoj.1ee95969b4d2448a9e1b573a6851bffe
Document Type :
article
Full Text :
https://doi.org/10.2298/SARH211118013R