Pharmacogenetic testing: current state of the issue
DOI:
https://doi.org/10.14739/2409-2932.2024.3.310994Keywords:
pharmacogenetics, personalized medicine, drug metabolism, cytochrome P450, pharmacogenetic testing, adverse drug events, clinical practice, genetic polymorphisms, drug safety, healthcare, pharmacogenomics, genetic testing, precision medicineAbstract
Aim. The purpose of this work is to emphasize the importance and practical benefits of pharmacogenetics in medicine, demonstrating how the integration of pharmacogenetics into clinical practice can improve treatment outcomes and enhance the safety of therapies.
Pharmacogenetics is a rapidly developing branch of pharmacology that studies how genetic variation affects an individual’s response to drugs. By understanding these genetic differences, healthcare providers can tailor drug therapy to maximize efficacy and minimize adverse drug reactions. The field aims to move away from the traditional one-size-fits-all approach and instead personalize medical treatment based on a person’s genetic makeup. The ability to predict a person’s response to medication based on their genetic profile has profound implications. For example, pharmacogenetic testing can identify patients at risk for life-threatening adverse drug reactions, such as drug-induced liver injury. This proactive approach can prevent adverse events, improving patient safety and the overall quality of care. In addition, pharmacogenetics aids in the development of new drugs by identifying genetic markers associated with drug responses, optimizing the drug development process, and reducing the time and costs associated with bringing new drugs to market. Key advances in pharmacogenetics include the identification of genetic polymorphisms in enzymes, such as cytochrome P450, that affect drug metabolism, thereby influencing both safety and efficacy. Pharmacogenetic testing allows doctors to predict the best drug and dosage for a patient, improving treatment outcomes and reducing the risk of adverse drug events.
Despite its potential, the integration of pharmacogenetics into clinical practice faces challenges, including a lack of reliable clinical evidence, inadequate physician education, and the need for a comprehensive health IT infrastructure to support the use of genetic data. Ethical and legal issues, such as patient privacy and the risk of genetic discrimination, also present significant obstacles. However, continued research, the development of genetic testing technologies, and interdisciplinary collaborations are paving the way for more widespread adoption of pharmacogenetics, which promises to significantly improve patient care and healthcare efficiency. Key resources such as PharmGKB, CPIC, and the NIH provide valuable information and guidance for clinicians, researchers, and students, helping bridge the gap between genetics research and clinical application.
Conclusions. Pharmacogenetics represents a significant advancement in personalized medicine, offering the potential to tailor drug therapies to individual genetic profiles. Although the field has made substantial progress, challenges remain in the form of insufficient clinical evidence, implementation barriers, and ethical concerns. Continued research and collaboration among stakeholders are essential to fully realize the benefits of pharmacogenetic testing in clinical practice.
References
Velasco-Ruiz A, Nuñez-Torres R, Pita G, Wildiers H, Lambrechts D, Hatse S, et al. POLRMT as a Novel Susceptibility Gene for Cardiotoxicity in Epirubicin Treatment of Breast Cancer Patients. Pharmaceutics. 2021;13(11):1942. doi: https://doi.org/10.3390/pharmaceutics13111942
Phuong Nhung V, Dang Ton N, Van Hai N, Hai Ha N. Genetic variation of pharmacogenes. Vietnam Journal of Biotechnology. 2020;18(3):393-416. doi: https://doi.org/10.15625/1811-4989/18/3/14972
Li-Wan-Po A. Pharmacogenetics and personalized medicine. J Clin Pharm Ther. 2012;37(6):617-9. doi: https://doi.org/10.1111/jcpt.12010
Beauchamp GA, Amaducci A, Greenberg MR, Meyers M, Cook M, Cannon RD, et al. Adverse drug events and reactions managed by medical toxicologists: an analysis of the toxicology investigators consortium (toxic) registry, 2010-2016. J Med Toxicol. 2019;15(4):262-70. doi: https://doi.org/10.1007/s13181-019-00719-w
Hakooz N. Pharmacogenetics and personalized medicines. Jordan J Pharm Sci. 2023;16(2):444. doi: https://doi.org/10.35516/jjps.v16i2.1483
Ruwali M. Pharmacogenetics and Cancer Treatment: Progress and Prospects [Internet]. Molecular Medicine. IntechOpen; 2019. Available from: https://doi.org/10.5772/intechopen.83424
Farhat K. Pharmacogenetics- strengthening the clinical medicine. Pak Armed Forces Med J. 2022;72(5):1499-500. doi: https://doi.org/10.51253/pafmj.v72i5.9469
Beutler E, West C, Beutler B. Electrophoretic polymorphism of glutathione peroxidase. Ann Hum Genet. 1974;38(2):163-9. doi: https://doi.org/10.1111/j.1469-1809.1974.tb01947.x
Sepúlveda N, Grignard L, Curry J, Mahey L, Bastiaens GJ, Tiono AB, et al. G6PD polymorphisms and hemolysis after antimalarial treatment with low single-dose primaquine: a pooled analysis of six african clinical trials. Front Genet. 2021;12 :645688. doi: https://doi.org/10.3389/fgene.2021.645688
Tambe V, Sirsat B, Rajpoot K, Gadeval A, Tekade RK. Pharmacogenomics and drug metabolism. In: Biopharmaceutics and Pharmacokinetics Considerations: Volume 1 in Advances in Pharmaceutical Product Development and Research. Elsevier; 2021. doi: https://doi.org/10.1016/B978-0-12-814425-1.00021-8
Chamboko CR, Veldman W, Tata RB, Schoeberl B, Tastan Bishop Ö. Human cytochrome P450 1, 2, 3 families as pharmacogenes with emphases on their antimalarial and antituberculosis drugs and prevalent african alleles. Int J Mol Sci. 2023;24(4):3383. doi: https://doi.org/10.3390/ijms24043383
Austin-Zimmerman I, Wronska M, Wang B, Irizar H, Thygesen JH, Bhat A, et al. The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics. Genes. 2021;12(11):1758. doi: https://doi.org/10.3390/genes12111758
Ivanov HY, Grigorova D, Lauschke VM, Velinov B, Stoychev K, Kyosovska G, et al. CYP2C19 and CYP2D6 genotypes and metabolizer status distribution in a bulgarian psychiatric cohort. J Pers Med. 2022;12(7):1187. doi: https://doi.org/10.3390/jpm12071187
Sadee W, Wang D, Hartmann K, Toland AE. Pharmacogenomics: Driving Personalized Medicine. Pharmacol Rev. 2023;75(4):789-814. doi: https://doi.org/10.1124/pharmrev.122.000810
McInnes G, Yee SW, Pershad Y, Altman RB. Genomewide association studies in pharmacogenomics. Clin Pharmacol Amp Ther. 2021;110(3):637-48. doi: https://doi.org/10.1002/cpt.2349
Kehinde O, Ramsey LB, Gaedigk A, Oni-Orisan A. Advancing CYP2D6 Pharmacogenetics through a Pharmacoequity Lens. Clin Pharmacol Ther. 2023;114(1):69-76. doi: https://doi.org/10.1002/cpt.2890
Jafrin S, Naznin NE, Reza MS, Aziz MA, Islam MS. Risk of stroke in CYP2C19 LoF polymorphism carrier coronary artery disease patients undergoing clopidogrel therapy: an ethnicity-based updated meta-analysis. Eur J Intern Med. 2021;90:49-65. doi: https://doi.org/10.1016/j.ejim.2021.05.022
Somogyi AA, Athanasos P, White J, Bochner F, Ling W. Buprenorphine maintenance subjects are hyperalgesic and have no antinociceptive response to a very high morphine dose. Pain Med. 2020;21(9):2007-8. doi: https://doi.org/10.1093/pm/pnaa067
Johnson J, Caudle K, Gong L, Whirl-Carrillo M, Stein C, Scott S, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017;102(3):397-404. doi: https://doi.org/10.1002/cpt.668
Guedes A, Gomes CA, Martins S, Cruz R. Pharmacogenomic application in her2-positive breast cancer. Int J Clin Exp Med Res. 2021;5(4):490-7. doi: https://doi.org/10.26855/ijcemr.2021.10.011
Vo TN, Chu VS, Nguyen DT, Nguyen VL, Nguyen TV. Evaluating the effect of screening dual HLA-A*31:01 and HLA-B*15:02 alleles by multiplex real-time PCR technique on reducing the risk of Carbamazepine-induced hypersensitivity reactions. Minist Sci Technol Vietnam. 2023;65(5):36-42. doi: https://doi.org/10.31276/vjst.65(5).36-42
Roden DM, McLeod HL, Relling MV, Williams MS, Mensah GA, Peterson JF, et al. Pharmacogenomics. Lancet. 2019;394(10197):521-32. doi: https://doi.org/10.1016/s0140-6736(19)31276-0
Widjaja E. Gene panel to guide antiseizure medication prescribing: Does the cost justify the benefits? Epilepsia. 2022;63(12):3122-4. doi: https://doi.org/10.1111/epi.17418
Jin CD, Kim MH, Guo LZ, Jin E, Shin ES, Ann SH, et al. Pharmacodynamic study of prasugrel or clopidogrel in non-ST-elevation acute coronary syndrome with CYP2C19 genetic variants undergoing percutaneous coronary intervention (PRAISE-GENE trial). Int J Cardiol. 2020;305:11-7. doi: https://doi.org/10.1016/j.ijcard.2020.01.058
Zubiaur P, Saiz-Rodríguez M, Villapalos-García G, Navares-Gómez M, Koller D, Abad-Santos F. HCP5 rs2395029 is a rapid and inexpensive alternative to HLA-B*57:01 genotyping to predict abacavir hypersensitivity reaction in Spain. Pharmacogenet Genomics. 2021;31(3):53-9. doi: https://doi.org/10.1097/FPC.0000000000000421
Mao L, Zhao W, Li X, Zhang S, Zhou C, Zhou D, et al. Mutation spectrum of EGFR from 21,324 chinese patients with non-small cell lung cancer (NSCLC) successfully tested by multiple methods in a cap-accredited laboratory. Pathol Oncol Res. 2021;27:602726. doi: https://doi.org/10.3389/pore.2021.602726
Rucci F, Cigoli MS, Marini V, Fucile C, Mattioli F, Robbiano L, et al. Combined evaluation of genotype and phenotype of thiopurine S-methyltransferase (TPMT) in the clinical management of patients in chronic therapy with azathioprine. Drug Metab Pers Ther. 2019;34(1). doi: https://doi.org/10.1515/dmpt-2018-0037
Shahrure ZM, Irshaid YM, Mustafa KN, Abujbara MA, Al Shhab M, El-Khateeb MS, et al. SLCO1B1 Gene Polymorphisms (rs2306283 and rs4149056) and Statin-Induced Myopathy in Jordanian Diabetics. Curr Rev Clin Exp Pharmacol. 2021;16(3):281-8. doi: https://doi.org/10.2174/1574884715666200827105612
Bank S, Andersen PS, Burisch J, Pedersen N, Roug S, Galsgaard J, et al. Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy. Pharmacogenomics J. 2017;18(1):87-97. doi: https://doi.org/10.1038/tpj.2016.84
Duarte JD, Cavallari LH. Pharmacogenetics to guide cardiovascular drug therapy. Nat Rev Cardiol. 2021;18(9):649-65. doi: https://doi.org/10.1038/s41569-021-00549-w
Kurnat-Thoma E. Educational and ethical considerations for genetic test implementation within health care systems. Netw Syst Med. 2020;3(1):58-66. doi: https://doi.org/10.1089/nsm.2019.0010
Rogers SL, Keeling NJ, Giri J, Gonzaludo N, Jones JS, Glogowski E, et al. PARC report: a health-systems focus on reimbursement and patient access to pharmacogenomics testing. Pharmacogenomics. 2020;21(11):785-96. doi: https://doi.org/10.2217/pgs-2019-0192
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