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Rational Pharmacotherapy in Cardiology

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New Pharmacogenetic Markers to Predict the Risk of Bleeding During Taking of Direct Oral Anticoagulants

https://doi.org/10.20996/1819-6446-2020-10-05

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Abstract

Aim. To search for new pharmacogenetic biomarkers of bleeding risk in patients taking rivaroxaban and dabigatran for different indications: atrial fibrillation, endoprosthesis of large joints of lower limbs.

Material and methods. The study enrolled 29 patients (17 patients received dabigatran and 12 –rivaroxaban), who had hemorrhagic complications during taking direct oral anticoagulants. To find new pharmacogenetic biomarkers of bleeding risk, a next generation sequencing (NGS) was performed for selected candidate genes.

Results. Among the patients with bleeding who received dabigatran, 13 variants of the nucleotide sequence showed statistically significant deviation from the population values: 11 in the CES1 gene and 2 in the ABCB1 gene. Among the patients with bleeding who received rivaroxaban, 7 variants of nucleotide sequence showed significant deviation: 4 in the ABCG2 gene, 2 in the CYP3A4 gene, and 1 in the ABCB1 gene.

Conclusion. The identified in this study polymorphisms of candidate genes ABCB1, ABCG2, CES1, CYP3A4 were associated with the risk of bleeding in patients taking rivaroxaban and dabigatran. It makes an important contribution to the pharmacogenetics of direct oral anticoagulants and require additional assessment of clinical significance in further studies.

About the Authors

K. B. Mirzaev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Karin B. Mirzaev – MD, PhD, Senior Researcher, Head of Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine; Associate Professor, Chair of Clinical Pharmacology and Therapeutics

Barrikadnaya ul. 2/1-1, Moscow, 125993



D. V. Ivashchenko
Russian Medical Academy of Continuous Professional Education
Russian Federation

Dmitriy V. Ivashchenko – MD, PhD, Senior Researcher, Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine; Associate Professor, Chair of Child Psychiatry and Psychotherapy

Barrikadnaya ul. 2/1-1, Moscow, 125993



I. V. Volodin
Russian Medical Academy of Continuous Professional Education; Research Centre for Medical Genetics
Russian Federation

Ilya V. Volodin – Junior Researcher, Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education; Researcher, Laboratory of Epigenetics, Research Centre for Medical Genetics

Barrikadnaya ul. 2/1-1, Moscow, 125993, 

Moskvorechiye ul. 1, Moscow, 115522 



E. A. Grishina
Russian Medical Academy of Continuous Professional Education
Russian Federation

Elena A. Grishina – PhD (Biology), Associate Professor, Head of Department of Molecular Medicine, Director of Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow, 125993



K. A. Akmalova
Russian Medical Academy of Continuous Professional Education
Russian Federation

Kristina A. Akmalova – Researcher, Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow, 125993



A. A. Kachanova
Russian Medical Academy of Continuous Professional Education
Russian Federation

Anastasia A. Kachanova – Junior Researcher, Department of Molecular Medicine, Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow, 125993



A. I. Skripka
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Alena A. Skripka – MD, Post-Graduate Student, Chair of Faculty Therapy №1

Trubezkaya ul. 8-2, Moscow, 119991



R. M. Minnigulov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Radik M. Minnigulov – MD, Post-Graduate Student, Chair of Clinical Pharmacology and Internal Diseases

Trubezkaya ul. 8-2, Moscow, 119991



T. E. Morozova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Tatiana E. Morozova – MD, PhD, Professor, Head of Chair of General Medical Practice

Trubezkaya ul. 8-2, Moscow, 119991

 



O. A. Baturina
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Olga A. Baturina – MD, Post-Graduate Student, Chair of Cardiology, Functional and Sonographic Diagnostics

Trubezkaya ul. 8-2, Moscow, 119991

 



A. N. Levanov
Saratov State Medical University named after V.I. Razumovsky
Russian Federation

Alexander N. Levanov – MD, Assistant, Chair of Occupational Diseases, Hematology and Clinical Pharmacology

Bolshaya Kazachya ul. 112, Saratov, 410012

 



T. V. Shelekhova
Saratov State Medical University named after V.I. Razumovsky
Russian Federation

Tatiana V. Shelekhova – MD, PhD, Professor, Head of Chair of Occupational Diseases, Hematology and Clinical Pharmacology

Bolshaya Kazachya ul. 112, Saratov, 410012

 



A. I. Kalinkin
Research Centre for Medical Genetics
Russian Federation

Alexey I. Kalinkin – Researcher, Laboratory of Epigenetics

Moskvorechiye ul. 1, Moscow, 115522

 



D. A. Napalkov
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

DmitriyA. Napalkov – MD, PhD, Professor, Chair of Faculty Therapy №1

Trubezkaya ul. 8-2, Moscow, 119991



A. A. Sokolova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Anastasia A. Sokolova – MD, PhD, Associate Professor, Chair of Faculty Therapy №1

Trubezkaya ul. 8-2, Moscow, 119991

 



D. A. Andreev
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Denis A. Andreev – MD, PhD, Professor, Head of Chair of Cardiology, Functional and Sonographic Diagnostics

Trubezkaya ul. 8-2, Moscow, 119991

 



I. N. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Igor N. Sychev – MD, PhD, Associate Professor, Chair of Clinical Pharmacology and Therapeutics

Barrikadnaya ul. 2/1-1, Moscow, 125993

 



P. O. Bochkov
Russian Medical Academy of Continuous Professional Education
Russian Federation

Pavel O. Bochkov – PhD (Biology), Senior Researcher, Department of Personalized Medicine, Research Institute of Molecular and Personalized Medicine

Barrikadnaya ul. 2/1-1, Moscow, 125993

 



D. A. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Dmitriy A. Sychev – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Head of Chair of Clinical Pharmacology and Therapeutics, Rector

Barrikadnaya ul. 2/1-1, Moscow, 125993

 



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For citation:


Mirzaev K.B., Ivashchenko D.V., Volodin I.V., Grishina E.A., Akmalova K.A., Kachanova A.A., Skripka A.I., Minnigulov R.M., Morozova T.E., Baturina O.A., Levanov A.N., Shelekhova T.V., Kalinkin A.I., Napalkov D.A., Sokolova A.A., Andreev D.A., Sychev I.N., Bochkov P.O., Sychev D.A. New Pharmacogenetic Markers to Predict the Risk of Bleeding During Taking of Direct Oral Anticoagulants. Rational Pharmacotherapy in Cardiology. 2020;16(5):670-677. https://doi.org/10.20996/1819-6446-2020-10-05

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)