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 : Pharmacogenetics and Genomics

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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

Sychev, Dmitry Alekseevitcha; Sokolov, Aleksey Vladimirovichb; Reshetko, Olga Vilorovnab; Fisenko, Vladimir Petrovichc; Sychev, Igor Nikolaevicha; Grishina, Elena Anatolievnad; Bochkov, Pavel Olegoviche; Shevchenko, Roman Vladimiroviche; Abdullaev, Sherzod Pardaboevichf; Denisenko, Natalia Pavlovnae; Ivashchenko, Dmitry Vladimirovichg; Sozaeva, Zhannet Alimovnah; Kachanova, Anastasia Alekseevnah

Author Information

aDepartment 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

bDepartment 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

cDepartment 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

dFederal State Budgetary Educational Institution of Further Professional Education “Russian Medical Academy of Continuous Professional Education” of the Ministry of Healthcare of the Russian Federation

eDepartment 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

fDepartment 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

gResearch 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

hDepartment 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

Correspondence to: Aleksey Vladimirovich Sokolov, MD, 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, Bolshaya Kazachya str, 112, bldg. 2, Saratov, Russian Federation, 410012, Tel: +791 9836 5612; e-mail: [email protected]

Pharmacogenetics and Genomics 32(9):p 301-307, December 2022. | DOI: 10.1097/FPC.0000000000000483

Abstract

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.

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