Influence of ABCB1, CYP3A5 and CYP3A4 gene polymorphisms on prothrombin time and the residual equilibrium concentration of rivaroxaban in patients with non-valvular atrial fibrillation in real clinical practice.

Autor:	Sychev DA; Department of Pharmacology, Federal State Budgetary Educational Institution of Higher Professional Education 'Saratov State Medical University named after V.I.Razumovsky' of the Ministry of Healthcare of the Russian Federation., Sokolov AV; Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Rector of Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Reshetko OV; Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Rector of Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Fisenko VP; Department of Pharmacology of the Institute of Biodesign and Modeling of Complex Systems of Science and Technology Park of Biomedicine, Federal State Autonomous Educational Institution of Higher Professional Education 'First Moscow State Medical University named after I.M. Sechenov (Sechenov University)' of the Ministry of Healthcare of the Russian Federation., Sychev IN; Department of Pharmacology, Federal State Budgetary Educational Institution of Higher Professional Education 'Saratov State Medical University named after V.I.Razumovsky' of the Ministry of Healthcare of the Russian Federation., Grishina EA; Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Bochkov PO; Department of Personalized Medicine, Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Shevchenko RV; Department of Personalized Medicine, Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Abdullaev SP; Department of Molecular Medicine of Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Health of the Russian Federation., Denisenko NP; Department of Personalized Medicine, Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Ivashchenko DV; Research Laboratory of Genomic Predictors of Adverse Drug Reactions at the Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation., Sozaeva ZA; Department of Molecular Medicine, Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation., Kachanova AA; Department of Molecular Medicine, Research Centre of Molecular and Personalized Medicine, Federal State Budgetary Educational Institution of Further Professional Education 'Russian Medical Academy of Continuous Professional Education' of the Ministry of Healthcare of the Russian Federation, Moscow, Russian Federation.
Jazyk:	angličtina
Zdroj:	Pharmacogenetics and genomics [Pharmacogenet Genomics] 2022 Dec 01; Vol. 32 (9), pp. 301-307. Date of Electronic Publication: 2022 Oct 13.
DOI:	10.1097/FPC.0000000000000483
Abstrakt:	Objective: The study of ABCB1 and CYP3A4/3A5 gene polymorphism genes is promising in terms of their influence on prothrombin time variability, the residual equilibrium concentration of direct oral anticoagulants (DOACs) in patients with atrial fibrillation and the development of new personalized approaches to anticoagulation therapy in these patients. The aim of the study is to evaluate the effect of ABCB1 (rs1045642) C>T; ABCB1 (rs4148738) C>T and CYP3A5 (rs776746) A>G, CYP3A4*22(rs35599367) C>T gene polymorphisms on prothrombin time level and residual equilibrium concentration of rivaroxaban in patients with atrial fibrillation. Methods: In total 86 patients (42 men and 44 female), aged 67.24 ± 1.01 years with atrial fibrillation were enrolled in the study. HPLC mass spectrometry analysis was used to determine rivaroxaban residual equilibrium concentration. Prothrombin time data were obtained from patient records. Results: The residual equilibrium concentration of rivaroxaban in patients with ABCB1 rs4148738 CT genotype is significantly higher than in patients with ABCB1 rs4148738 CC (P  = 0.039). The analysis of the combination of genotypes did not find a statistically significant role of combinations of alleles of several polymorphic markers in increasing the risk of hemorrhagic complications when taking rivaroxaban. Conclusion: Patients with ABCB1 rs4148738 CT genotype have a statistically significantly higher residual equilibrium concentration of rivaroxaban in blood than patients with ABCB1 rs4148738 CC genotype, which should be considered when assessing the risk of hemorrhagic complications and risk of drug-drug interactions. Further studies of the effect of rivaroxaban pharmacogenetics on the safety profile and efficacy of therapy are needed. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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