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Фармакогенетика варфарина: обзор литературы
Фармакогенетика варфарина: обзор литературы
Изможерова Н.В., Шамбатов М.А., Попов А.А., Жук Д.Е., Солодченко В.А. Фармакогенетика варфарина: обзор литературы // CardioСоматика. 2024. Т. 15, № 3. С. 211–220. DOI: https://doi.org/10.17816/CS631885
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Аннотация
Варфарин представляет собой пероральный антикоагулянт непрямого действия, который широко применяется для предотвращения тромбоэмболических явлений. Наиболее перспективным подходом к персонализации использования непрямых антикоагулянтов является фармакогенетическое тестирование. Цель данного обзора — предоставление сведений о том, как генетическая предрасположенность больных влияет на фармакокинетику варфарина, что определяет разные режимы дозирования у пациентов. Для правильной интерпретации данных в клинических условиях необходимо разработать алгоритмы выбора оптимального режима дозирования, учитывающие возраст, пол, вес, рост, состояние здоровья и генетические особенности пациента. Эти алгоритмы помогают определить оптимальную дозу, повышают приверженность пациента к лечению и уверенность врача в безопасности терапии. Алгоритмы, учитывающие SNP в генах CYP2C9, VKORC1 и CYP4F2, более эффективны в прогнозировании доз варфарина, но их эффективность варьирует в зависимости от расовой принадлежности.
Ключевые слова: варфарин, фармакогенетика, CYP2C9, VKORC1, CYP4F2
Keywords: warfarin; pharmacogenetics, CYP2C9, VKORC1, CYP4F2
Ключевые слова: варфарин, фармакогенетика, CYP2C9, VKORC1, CYP4F2
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Keywords: warfarin; pharmacogenetics, CYP2C9, VKORC1, CYP4F2
Полный текст
Список литературы
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21. Caldwell MD, Berg RL, Zhang KQ, et al. Evaluation of genetic factors for warfarin dose prediction. Clin Med Res. 2007;5(1):8–16. doi: 10.3121/cmr.2007.724
22. Shalia KK, Doshi SM, Parikh S, et al. Prevalence of VKORC1 and CYP2C9 gene polymorphisms in Indian population and its effect on warfarin response. J Assoc Physicians India. 2012;60:34–38.
23. Li X, Li D, Wu JC, et al. Precision dosing of warfarin: open questions and strategies. Pharmacogenomics J. 2019;19(3):219–229. doi: 10.1038/s41397-019-0083-3
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27. Nakamura K, Obayashi K, Araki T, et al. CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. J Clin Pharm Ther. 2012;37(4):481–485. doi: 10.1111/j.1365-2710.2011.01317.x
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doi: 10.1038/clpt.2008.10
29. Asiimwe IG, Zhang EJ, Osanlou R, et al. Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis. Clin Pharmacol Ther. 2020;107(6):1420–1433. doi: 10.1002/cpt.1755
30. Wang ZQ, Zhang R, Zhang PP, et al. Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol. 2015;65(4):364–370. doi: 10.1097/FJC.0000000000000204
31. Dobrzanski S, Duncan SE, Harkiss A, Wardlaw A. Age and weight as determinants of warfarin requirements. J Clin Hosp Pharm. 1983;8(1):75–77.
doi: 10.1111/j.1365-2710.1983.tb00899.x
32. Redwood M, Taylor C, Bain BJ, Matthews JH. The association of age with dosage requirement for warfarin. Age Ageing. 1991;20(3):217–220. doi: 10.1093/ageing/20.3.217
33. Gurwitz JH, Avorn J, Ross-Degnan D, et al. Aging and the anticoagulant response to warfarin therapy. Ann Intern Med. 1992;116(11):901–904. doi: 10.7326/0003-4819-116-11-901
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doi: 10.1002/phar.2089
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36. Tellor KB, Nguyen SN, Bultas AC, et al. Evaluation of the impact of body mass index on warfarin requirements in hospitalized patients. Ther Adv Cardiovasc Dis. 2018;12(8):207–216. doi: 10.1177/1753944718781295
37. Absher RK, Moore ME, Parker MH. Patient-specific factors predictive of warfarin dosage requirements. Ann Pharmacother. 2002;36(10):1512–1517. doi: 10.1345/aph.1C025
38. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S–e88S. doi: 10.1378/chest.11-2292
39. Salem M, Eljilany I, El-Bardissy A, Elewa H. Genetic Polymorphism Effect on Warfarin-Rifampin Interaction: A Case Report and Review of Literature. Pharmgenomics Pers Med. 2021;14:149–156. doi: 10.2147/PGPM.S288918
40. Wang M, Zeraatkar D, Obeda M, et al. Drug-drug interactions with warfarin: A systematic review and meta-analysis. Br J Clin Pharmacol. 2021;87(11):4051–4100.
doi: 10.1111/bcp.14833
41. Wong W, Wilson Norton J, Wittkowsky AK. Influence of warfarin regimen type on clinical and monitoring outcomes in stable patients in an anticoagulation management services. Pharmacotherapy. 1999;19(12):1385–1391. doi: 10.1592/phco.19.18.1385.30894
42. Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 Update. Clin Pharmacol Ther. 2017;102(3):397–404. doi: 10.1002/cpt.668
43. Zhang JE, Jorgensen AL, Alfirevic A, et al. Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in patients initiated on warfarin therapy. Pharmacogenet Genomics. 2009;19(10):781–789. doi: 10.1097/FPC.0b013e3283311347
44. Danese E, Raimondi S, Montagnana M, et al. Effect of CYP4F2, VKORC1, and CYP2C9 in influencing coumarin dose: A single-patient data meta-analysis in more than 15,000 individuals. Clin Pharmacol Ther. 2019;105(6):1477–1491. doi: 10.1002/cpt.1323
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3. Sychev DA, Ivashchenko DV, Rusin IV. Impact of pharmacogenetic testing on the risk of bleedings and excessive hypocoagulation episodes in the use of warfarin: The first meta-analysis of Russian prospective studies. Terapevticheskii Arkhiv. 2014;86(4):64–71. EDN: SVPGNB
4. Biss TT, Avery PJ, Brandão LR, et al. VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children. Blood. 2012;119(3):868–873. doi: 10.1182/blood-2011-08-372722
5. Kim SY, Kang JY, Hartman JH, et al. Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins. Drug Metab Lett. 2012;6(3):157–164.
doi: 10.2174/1872312811206030002
6. Almas T, Muhammad F, Siddiqui L, et al. Safety and efficacy of direct oral anticoagulants in comparison with warfarin across different BMI ranges: A systematic review and meta-analysis. Ann Med Surg (Lond). 2022;77:103610. doi: 10.1016/j.amsu.2022.103610
7. Tideman PA, Tirimacco R, St John A, Roberts GW. How to manage warfarin therapy. Aust Prescr. 2015;38(2):44–48. doi: 10.18773/austprescr.2015.016
8. Duarte JD, Cavallari LH. Pharmacogenetics to guide cardiovascular drug therapy. Nat Rev Cardiol. 2021;18(9):649–665. doi: 10.1038/s41569-021-00549-w
9. Adcock DM, Koftan C, Crisan D, Kiechle FL. Effect of polymorphisms in the cytochrome P450 CYP2C9 gene on warfarin anticoagulation. Arch Pathol Lab Med.
2004;128(12):1360–1363. doi: 10.5858/2004-128-1360-EOPITC
10. Jia L, Wang Z, Men J, et al. Polymorphisms of VKORC1 and CYP2C9 are associated with warfarin sensitivity in Chinese population. Ther Clin Risk Manag. 2017;13:421–425.
doi: 10.2147/TCRM.S130198
11. Daly AK, Rettie AE, Fowler DM, Miners JO. Pharmacogenomics of CYP2C9: Functional and Clinical Considerations. J Pers Med. 2017;8(1):1. doi: 10.3390/jpm8010001
12. Fihn SD, Callahan CM, Martin DC, et al. The risk for and severity of bleeding complications in elderly patients treated with warfarin. The National Consortium of Anticoagulation Clinics. Ann Intern Med. 1996;124(11):970–979. doi: 10.7326/0003-4819-124-11-199606010-00004
13. Moyer TP, O'Kane DJ, Baudhuin LM, et al. Warfarin sensitivity genotyping: a review of the literature and summary of patient experience. Mayo Clin Proc. 2009;84(12):1079–1094.
doi: 10.4065/mcp.2009.0278
14. Perini JA, Struchiner CJ, Silva-Assunção E, et al. Pharmacogenetics of warfarin: development of a dosing algorithm for brazilian patients. Clin Pharmacol Ther. 2008;84(6):722–728. doi: 10.1038/clpt.2008.166
15. Asiimwe IG, Zhang EJ, Osanlou R, et al. Warfarin dosing algorithms: A systematic review. Br J Clin Pharmacol. 2021;87(4):1717–1729. doi: 10.1111/bcp.14608
16. Limdi NA, Wadelius M, Cavallari L, et al. Warfarin pharmacogenetics: a single VKORC1 polymorphism is predictive of dose across 3 racial groups. Blood. 2010;115(18):3827–3834. doi: 10.1182/blood-2009-12-255992
17. Sridharan K, Al Banna R, Malalla Z, et al. Influence of CYP2C9, VKORC1, and CYP4F2 polymorphisms on the pharmacodynamic parameters of warfarin: a cross-sectional study. Pharmacol Rep. 2021;73(5):1405–1417. doi: 10.1007/s43440-021-00256-w
18. Sambialova AYu, Bairova TA, Belyaeva EV, et al. Polymorphism of CYP2C9, CYP4F2, VKORC1 genes in the Buryat population. Russian Journal of Genetics. 2020;56(12):1427–34.
doi: 10.31857/S0016675820120127
19. Akdeniz CS, Cevik M, Canbolat IP, et al. The effects of CYP2C9 and VKORC1 gene polymorphisms on warfarin maintenance dose in Turkish cardiac patients. Future Cardiol. 2020;16(6):645–654. doi: 10.2217/fca-2020-0027
20. Farzamikia N, Sakhinia E, Afrasiabirad A. pharmacogenetics-based warfarin dosing in patients with cardiac valve replacement: The effects of CYP2C9 and VKORC1 gene polymorphisms. Lab Med. 2017;49(1):25–34. doi: 10.1093/labmed/lmx072
21. Caldwell MD, Berg RL, Zhang KQ, et al. Evaluation of genetic factors for warfarin dose prediction. Clin Med Res. 2007;5(1):8–16. doi: 10.3121/cmr.2007.724
22. Shalia KK, Doshi SM, Parikh S, et al. Prevalence of VKORC1 and CYP2C9 gene polymorphisms in Indian population and its effect on warfarin response. J Assoc Physicians India. 2012;60:34–38.
23. Li X, Li D, Wu JC, et al. Precision dosing of warfarin: open questions and strategies. Pharmacogenomics J. 2019;19(3):219–229. doi: 10.1038/s41397-019-0083-3
24. Caldwell MD, Awad T, Johnson JA, et al. CYP4F2 genetic variant alters required warfarin dose. Blood. 2008;111(8):4106–4112. doi: 10.1182/blood-2007-11-122010
25. Al-Eitan LN, Almasri AY, Alnaamneh AH, et al. Influence of CYP4F2, ApoE, and CYP2A6 gene polymorphisms on the variability of Warfarin dosage requirements and susceptibility to cardiovascular disease in Jordan. Int J Med Sci. 2021;18(3):826–834. doi: 10.7150/ijms.51546
26. Jarrar Y, Alkhalili M, Alhawari H, et al. The frequency of cytochrome 4F2 rs2108622 genetic variant and its effects on the lipid profile and complications of type II diabetes among a sample of patients in Jordan: A pilot study. Prostaglandins Other Lipid Mediat. 2023;165:106715. doi: 10.1016/j.prostaglandins.2023.106715
27. Nakamura K, Obayashi K, Araki T, et al. CYP4F2 gene polymorphism as a contributor to warfarin maintenance dose in Japanese subjects. J Clin Pharm Ther. 2012;37(4):481–485. doi: 10.1111/j.1365-2710.2011.01317.x
28. Gage BF, Eby C, Johnson JA, et al. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther. 2008;84(3):326–331.
doi: 10.1038/clpt.2008.10
29. Asiimwe IG, Zhang EJ, Osanlou R, et al. Genetic Factors Influencing Warfarin Dose in Black-African Patients: A Systematic Review and Meta-Analysis. Clin Pharmacol Ther. 2020;107(6):1420–1433. doi: 10.1002/cpt.1755
30. Wang ZQ, Zhang R, Zhang PP, et al. Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol. 2015;65(4):364–370. doi: 10.1097/FJC.0000000000000204
31. Dobrzanski S, Duncan SE, Harkiss A, Wardlaw A. Age and weight as determinants of warfarin requirements. J Clin Hosp Pharm. 1983;8(1):75–77.
doi: 10.1111/j.1365-2710.1983.tb00899.x
32. Redwood M, Taylor C, Bain BJ, Matthews JH. The association of age with dosage requirement for warfarin. Age Ageing. 1991;20(3):217–220. doi: 10.1093/ageing/20.3.217
33. Gurwitz JH, Avorn J, Ross-Degnan D, et al. Aging and the anticoagulant response to warfarin therapy. Ann Intern Med. 1992;116(11):901–904. doi: 10.7326/0003-4819-116-11-901
34. Shendre A, Parmar GM, Dillon C, et al. Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage. Pharmacotherapy. 2018;38(6):588–596.
doi: 10.1002/phar.2089
35. Mueller JA, Patel T, Halawa A, et al. Warfarin dosing and body mass index. Ann Pharmacother. 2014;48(5):584–588. doi: 10.1177/1060028013517541
36. Tellor KB, Nguyen SN, Bultas AC, et al. Evaluation of the impact of body mass index on warfarin requirements in hospitalized patients. Ther Adv Cardiovasc Dis. 2018;12(8):207–216. doi: 10.1177/1753944718781295
37. Absher RK, Moore ME, Parker MH. Patient-specific factors predictive of warfarin dosage requirements. Ann Pharmacother. 2002;36(10):1512–1517. doi: 10.1345/aph.1C025
38. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S–e88S. doi: 10.1378/chest.11-2292
39. Salem M, Eljilany I, El-Bardissy A, Elewa H. Genetic Polymorphism Effect on Warfarin-Rifampin Interaction: A Case Report and Review of Literature. Pharmgenomics Pers Med. 2021;14:149–156. doi: 10.2147/PGPM.S288918
40. Wang M, Zeraatkar D, Obeda M, et al. Drug-drug interactions with warfarin: A systematic review and meta-analysis. Br J Clin Pharmacol. 2021;87(11):4051–4100.
doi: 10.1111/bcp.14833
41. Wong W, Wilson Norton J, Wittkowsky AK. Influence of warfarin regimen type on clinical and monitoring outcomes in stable patients in an anticoagulation management services. Pharmacotherapy. 1999;19(12):1385–1391. doi: 10.1592/phco.19.18.1385.30894
42. Johnson JA, Caudle KE, Gong L, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 Update. Clin Pharmacol Ther. 2017;102(3):397–404. doi: 10.1002/cpt.668
43. Zhang JE, Jorgensen AL, Alfirevic A, et al. Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in patients initiated on warfarin therapy. Pharmacogenet Genomics. 2009;19(10):781–789. doi: 10.1097/FPC.0b013e3283311347
44. Danese E, Raimondi S, Montagnana M, et al. Effect of CYP4F2, VKORC1, and CYP2C9 in influencing coumarin dose: A single-patient data meta-analysis in more than 15,000 individuals. Clin Pharmacol Ther. 2019;105(6):1477–1491. doi: 10.1002/cpt.1323
45. Klein TE, Altman RB, Eriksson N, et al.; International Warfarin Pharmacogenetics Consortium. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360(8):753–764. doi: 10.1056/NEJMoa0809329
Авторы
Н.В. Изможерова*, М.А. Шамбатов, А.А. Попов, Д.Е. Жук, В.А. Солодченко
Уральский государственный медицинский университет, Екатеринбург, Россия
*nadezhda_izm@mail.ru
Ural State Medical University, Yekaterinburg, Russia
*nadezhda_izm@mail.ru
Уральский государственный медицинский университет, Екатеринбург, Россия
*nadezhda_izm@mail.ru
________________________________________________
Ural State Medical University, Yekaterinburg, Russia
*nadezhda_izm@mail.ru
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