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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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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Review
For citations:
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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