Email this article Pharmacogenetics of new oral anticoagulants
- Authors: Azimova B.A.1,2, Nikolayev K.Y.2,3, Vorobyov A.S.1,2, Urvantseva I.A.1,2
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Affiliations:
- District Cardiological Dispensary Center for Diagnostics and Cardiovascular Surgery
- Surgut State University
- Research Institute of Therapy and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of RAS
- Issue: Vol 13, No 3 (2022)
- Pages: 162-167
- Section: Reviews
- URL: https://journals.rcsi.science/2221-7185/article/view/134173
- DOI: https://doi.org/10.17816/CS107195
- ID: 134173
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Abstract
The review presents modern studies the effect of genetic polymorphisms on the efficienty and safety of therapy with new oral anticoagulants. Hepatic carboxylesterase encoded by the CES1 gene and P-glycoprotein encoded by the ABCB1 gene affect dabigatran pharmacokinetics. The role of glucuronidation enzymes (UGT2B15, UGT1A9, UGT2B7) involved in active dabigatran metabolism is poorly understood. An increase in the peak apixaban concentration was noted in patients with the rs4148738 polymorphism of the ABCB1 gene. Polymorphisms rs776746 and rs77674 of the CYP3A5 gene affect concentration of apixaban in Asian patients and thus increased the bleeding risk. The effect SULT1A1 sulfotransferase on the metabolism of apixaban has yet to be studied. The BCRP protein encoded by the ABCG2 gene is a poorly studied but promising direction for the pharmacokinetics of apixaban. ABCB1 and CYP3A4 of the cytochrome P450 system affect the rivaroxaban metabolism, however, the number of studies devoted to examining the effect of polymorphisms of these genes on the rivaroxaban pharmacokinetics limited. Thus, large studies are needed to clarify the clinical relevance of genotyping in target patients taking new oral anticoagulants.
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##article.viewOnOriginalSite##About the authors
Bella A. Azimova
District Cardiological Dispensary Center for Diagnostics and Cardiovascular Surgery; Surgut State University
Email: bella_azimova_surgut@mail.ru
ORCID iD: 0000-0003-3190-3782
graduate student
Russian Federation, 1 Lenin Ave., 628403, Surgut; SurgutKonstsantin Yu. Nikolayev
Surgut State University; Research Institute of Therapy and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics, Siberian Branch of RAS
Email: nikolaevky@yandex.ru
ORCID iD: 0000-0003-4601-6203
SPIN-code: 6638-2290
MD, D. Sci. (Med.), Prof., laboratory head
Russian Federation, 1, Lenina Ave., Surgut, 628400; NovosibirskAnton S. Vorobyov
District Cardiological Dispensary Center for Diagnostics and Cardiovascular Surgery; Surgut State University
Email: a.s.vorobyov@google.com
ORCID iD: 0000-0001-7014-2096
SPIN-code: 1756-6168
MD, Cand. Sci. (Med.), Assoc. Prof., leading reseacher
Russian Federation, 1, Lenina Ave., Surgut, 628400; SurgutIrina A. Urvantseva
District Cardiological Dispensary Center for Diagnostics and Cardiovascular Surgery; Surgut State University
Author for correspondence.
Email: priem@cardioc.ru
ORCID iD: 0000-0002-5545-9826
SPIN-code: 3495-6523
MD, Cand. Sci. (Med.), department head, chief physician
Russian Federation, 1, Lenina Ave., Surgut, 628400; SurgutReferences
- Savinova AV, Dobrodeeva VS, Petrova MM, et al. Pharmacokinetics and Pharmacogenetics of Dabigatran. Rational Pharmacotherapy in Cardiology. 2021;17(1):146–152. (In Russ). doi: 10.20996/1819-6446-2021-01-04
- Savinova AV, Petrova MM, Shnayder NA, et al. Pharmacokinetics and Pharmacogenetics of Apixaban. Rational Pharmacotherapy in Cardiology. 2020;16(5):852–860. (In Russ). doi: 10.20996/1819-6446-2020-10-1
- Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–2352. doi: 10.1056/NEJMoa0906598
- Ross S, Pare G. Pharmacogenetics of antiplatelets and anticoagulants: a report on clopidogrel, warfarin and dabigatran. Pharmacogenomics. 2013;14(13):1565–1572. doi: 10.2217/pgs.13.149
- Mirzaev KB, Ivashchenko DV, Volodin IV, et al. New Pharmacogenetic Markers to Predict the Risk of Bleeding During Taking of Direct Oral Anticoagulants. Rational Pharmacotherapy in Cardiology. 2020;16(5):670–677. (In Russ). doi: 10.20996/1819-6446-2020-10-05
- Alfirevic A, Downing J, Daras K, et al. Has the introduction of direct oral anticoagulants (DOACs) in England increased emergency admissions for bleeding conditions? A longitudinal ecological study. BMJ Open. 2020;10(5):e033357. doi: 10.1136/bmjopen-2019-033357
- Abdullaev ShP, Mirzayev KB, Mammaev SN, et al. The prevalence of the polymorphic marker rs2244613 of the CES1 gene associated with a lower risk of bleeding in patients using dabigatran in russians and in the three ethnic groups of the republic of Dagestan. Clinical Pharmacology and Therapy. 2018;4:87–90. (In Russ).
- Kryukov AV, Sychev DA, Tereshchenko OV. Pharmacogenetic Aspects of New Oral Anticoagulants Application. Rational Pharmacotherapy in Cardiology. 2017;13(3):416–421. (In Russ). doi: 10.20996/1819-6446-2017-13-3-416-421
- Ebner T, Wagner K, Wienen W. Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010;38(9):1567–1575. doi: 10.1124/dmd.110.033696
- Carlini EJ, Raftogianis RB, Wood TC, et al. Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects. Pharmacogenetics. 2001;11(1):57–68. doi: 10.1097/00008571-200102000-00007
- Ragia G, Manolopoulos VG. Pharmacogenomics of anticoagulation therapy: the last 10 years. Pharmacogenomics. 2019;20(16):1113–1117. doi: 10.2217/pgs-2019-0149
- Paré G, Eriksson N, Lehr T, et al. Genetic determinants of dabigatran plasma levels and their relation to bleeding. Circulation. 2013;127(13):1404–1412. doi: 10.1161/CIRCULATIONAHA
- Dimatteo C, D'Andrea G, Vecchione G, et al. Pharmacogenetics of dabigatran etexilate interindividual variability. Thromb Res. 2016;144:1–5. doi: 10.1016/j.thromres.2016.05.025
- Ji Q, Zhang C, Xu Q, et al. The impact of ABCB1 and CES1 polymorphisms on dabigatran pharmacokinetics and pharmacodynamics in patients with atrial fibrillation. Br J Clin Pharmacol. 2020;87(5):2247–2255. doi: 10.1111/bcp.14646
- Gouin-Thibault I, Delavenne X, Blanchard A, et al. Interindividual variability in dabigatran and rivaroxaban exposure: contribution of ABCB1 genetic polymorphisms and interaction with clarithromycin. J Thromb Haemost. 2017;15(2):273–283. doi: 10.1111/bcp.14646
- Sychev DA, Levanov AN, Shelehova TV, et al. Impact of ABCB1 and CES1 genetic polymorphisms on trough steady-state dabigatran concentrations in patients after endoprosthesis of knife join. Atherothrombosis. 2018;(1):122–130. (In Russ). doi: 10.21518/2307-1109-2018-1-122-130
- Xie Q, Xiang Q, Mu G, et al. Effect of ABCB1 Genotypes on the Pharmacokinetics and Clinical Outcomes of New Oral Anticoagulants: A Systematic Review and Meta-analysis. Curr Pharm Des. 2018;24(30):3558–3565. doi: 10.2174/1381612824666181018153641
- Raymond J, Imbert L, Cousin T, et al. Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review. J Pers Med. 2021;11(1):37. doi: 10.3390/jpm11010037
- He X, Hesse LM, Hazarika S, et al. Evidence for oxazepam as an in vivo probe of UGT2B15: oxazepam clearance is reduced by UGT2B15 D85Y polymorphism but unaffected by UGT2B17 deletion. Br J Clin Pharmacol. 2009;68(5):721–730. doi: 10.1111/j.1365-2125.2009.03519.x
- Dimatteo C, D’Andrea G, Vecchione G, et al. ABCB1 SNP rs4148738 modulation of apixaban interindividual variability. Thromb Res. 2016;145:24–26. doi: 10.1016/j.thromres.2016.07.005
- Kryukov AV, Sychev DA, Andreev DA, et al. The pharmacokinetics of apixaban in patients with cardioembolic stroke in acute phase. Rational Pharmacotherapy in Cardiology. 2016;12(3):253–259 (In Russ). doi: 10.20996/1819-6446-2016-12-3-253-259
- Ueshima S, Hira D, Fujii R, et al. Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation. Pharm Genom. 2017;27(9):329–336. doi: 10.1097/FPC.0000000000000294
- Nagar S, Walther S, Blanchard RL. Sulfotransferase (SULT) 1A1 polymorphic variants *1, *2, and *3 are associated with altered enzymatic activity, cellular phenotype, and protein degradation. Mol Pharmacol. 2006;69(6):2084–2092. doi: 10.1124/mol.105.019240
- Wang L, Raghavan N, He K, et al. Sulfation of o-demethyl apixaban: enzyme identification and species comparison. Drug Metab Dispos. 2009;37(4):802–808. doi: 10.1124/dmd.108.025593
- Cusatis G, Sparreboom A. Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008;9(8):1005–1009. doi: 10.2217/14622416.9.8.1005
- Gulilat M, Keller D, Linton B, et al. Drug interactions and pharmacogenetic factors contribute to variation in apixaban concentration in atrial fibrillation patients in routine care. J Thromb Thrombolysis. 2020;49(2):294–303. doi: 10.1007/s11239-019-01962-2
- Ing Lorenzini K, Daali Y, Fontana P, et al. Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect. Front Pharmacol. 2016;7:494. doi: 10.3389/fphar.2016.00494
- Sennesael AL, Larock AS, Douxfils J, et al. Rivaroxaban plasma levels in patients admitted for bleeding events: Insights from a prospective study. Thromb J. 2018;16:28. doi: 10.1186/s12959-018-0183-3
- Sychev D, Minnigulov R, Bochkov P, et al. Effect of CYP3A4, CYP3A5, ABCB1 gene polymorphisms on rivaroxaban pharmacokinetics in patients undergoing total hip and knee replacement surgery. High Blood Press Cardiovasc Prev. 2019;26(5):413–420. doi: 10.1007/s40292-019-00342-4
- Sweezy T, Mousa SA. Genotype-guided use of oral antithrombotic therapy: A pharmacoeconomic perspective. Per Med. 2014;11(2):223–235. doi: 10.2217/pme.13.106
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