Pharmacogenetics of cytochrome P450 as an important component of the pharmacological response to therapy with medications, affecting hemostasis processes

Abstract


This review considers the need to introduce pharmacogenetic testing for such groups of medications that affect hemostasis processes, such as antiplatelet agents and indirect anticoagulants. The presented facts demonstrate the need of introduction for pharmacogenetic testing into ongoing clinical practice for such drugs due to the increased risk of undesirable adverse reactions in carriers of cytochrome P450 polymorphisms. Attention is also given to the economic feasibility of pharmacogenetic testing in the context of treatment with the above-mentioned drugs.

About the authors

Nikolay L. Shimanovskii

N. I. Pirogov Russian National Research Medical University, Moscow, Russia; N. A. Semashko National Research Institute of Public Health, Moscow, Russian Federation; Plekhanov Russian University of Economics, Moscow, Russia

Email: shimannn@yandex.ru

Valentin E. Marievskii

N. I. Pirogov Russian National Research Medical University, Moscow, Russia

Email: valentinmarievskiy@yandex.ru

Marina M. Shegay

N. A. Semashko National Research Institute of Public Health, Moscow, Russian Federation

Email: mshegai@yandex.ru

Rustam R. Mukhamediev

N. A. Semashko National Research Institute of Public Health, Moscow, Russian Federation

Email: rustammukhamedievv@gmail.com

References

  1. Manikandan P, Nagini S. Cytochrome P450 structure, function and clinical significance: a review. Current Drug Targets. 2018;19(1):38—54.
  2. Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol. Sci. 2004;25(4):193—200.
  3. Meloche M, Khazaka M, Kassem I, et al. CYP2D6 polymorphism and its impact on the clinical response to metoprolol: a systematic review and meta-analysis. Br J Clin Pharmacol. 2020;86(6):1015—1033.
  4. Taylor C, Crosby I, Yip V, et al. A review of the important role of CYP2D6 in pharmacogenomics. Genes. 2020;11(11):1295.
  5. Ding Z, Kim S, Dorsam RT, et al. Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270. Blood. 2003;101(10):3908—3914.
  6. Sangkuhl K, Klein TE, Altman RB. Clopidogrel pathway. Pharmacogenet Genomics. 2010;20(7):463—465.
  7. Pratt VM, Del Tredici AL, Hachad H, et al. Recommendations for clinical CYP2C19 genotyping allele selection: a report of the Association for Molecular Pathology. J Mol Diagn. 2018;20(3):269—276.
  8. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354—362.
  9. Tousoulis D, Siasos G, Zaromytidou M, et al. The role of the cytochrome P450 polymorphisms in clopidogrel efficacy and clinical utility. Curr Med Chem. 2011;18(3):427—438.
  10. Mao L, Jian C, Changzhi L, et al. Cytochrome CYP2C19 polymorphism and risk of adverse clinical events in clopidogrel-treated patients: a meta-analysis based on 23,035 subjects. Arch Cardiovasc Dis. 2013;106(10):517—527.
  11. Bedair KF, Smith B, Palmer CNA, et al. Pharmacogenetics at scale in real-world bioresources: CYP2C19 and clopidogrel outcomes in UK Biobank. Pharmacogenet Genomics. 2024;34(3):73—82.
  12. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304(16):1821—1830.
  13. Mega JL, Hochholzer W, Frelinger AL 3rd, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA. 2011;306(20):2221—2228.
  14. Dobesh PP, Oestreich JH. Ticagrelor: pharmacokinetics, pharmacodynamics, clinical efficacy, and safety. Pharmacotherapy. 2014;34(10):1077—1090.
  15. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet. 2010;376(9749):1320—1328.
  16. Claassens DM, van Dorst PW, Vos GJ, et al. Cost effectiveness of a CYP2C19 genotype-guided strategy in patients with acute myocardial infarction: results from the POPular genetics trial. Am J Cardiovasc Drugs. 2022:22(2):195—206. doi: 10.1007/s40256-021-00496-4
  17. Castrichini M, Luzum JA, Pereira N. Pharmacogenetics of antiplatelet therapy. Annu Rev Pharmacol Toxicol. 2023;63(1):211—229.
  18. Wiviott SD, Antman EM. Clopidogrel resistance: a new chapter in a fast-moving story. Circulation. 2004;109(25):3064—3067.
  19. Wyatt J, Pettit W, Harirforoosh S. Pharmacogenetics of nonsteroidal anti-inflammatory drugs. Pharmacogenomics J. 2012;12(6):462—467.
  20. Agundez JA, Martinez C, Perez-Sala D, et al. Pharmacogenomics in aspirin intolerance. Curr Drug Metab. 2009;10(9):998—1008.
  21. Visscher H, Amstutz U, Sistonen J, et al. Pharmacogenomics of cardiovascular drugs and adverse effects in pediatrics. J Cardiovasc Pharmacol. 2011;58(3):228—239.
  22. Lane S, Al‐Zubiedi S, Hatch E, et al. The population pharmacokinetics of R‐and S‐warfarin: effect of genetic and clinical factors. Br J Clin Pharmacol. 2012;73(1):66—76.
  23. Wittkowsky AK. Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions. Semin Vasc Med. 2003;3(3):221—230. doi: 10.1055/s-2003-44457
  24. Johnson JA, Gong L, Whirl‐Carrillo M, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin Pharmacol Ther. 2011;90(4):625—629.
  25. Jiang NX, Ge JW, Xian YQ, et al. Clinical application of a new warfarin-dosing regimen based on the CYP2C9 and VKORC1 genotypes in atrial fibrillation patients. Biomed Rep. 2016;4(4):453—458.
  26. Gage BF, Bass AR, Lin H, et al. Effect of genotype-guided warfarin dosing on clinical events and anticoagulation control among patients undergoing hip or knee arthroplasty: the GIFT randomized clinical trial. JAMA. 2017;318(12):1115—1124.
  27. Eckman MH, Rosand J, Greenberg SM, Gage BF. Cost-effectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation. Ann Intern Med. 2009;150(2):73—83.
  28. Leey JA, McCabe S, Koch JA, Miles TP. Cost-effectiveness of genotype-guided warfarin therapy for anticoagulation in elderly patients with atrial fibrillation. Am J Geriatr Pharmacother. 2009;7(4):197—203.

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