CYP450 Gene Variations and Their Implications for Drug Response: A Pharmacogenomic Review
DOI:
https://doi.org/10.30872/jtpc.v10i2.434Keywords:
cytochrome P450, genetic variation, pharmacogenomic, phenoconversion, precision medicineAbstract
The Human Genome Project (HGP) has significantly advanced our understanding of how human genetic variation affects drug response, particularly through metabolic enzymes such as Cytochrome P450 (CYP450). This study aimed to explore the impact of genetic variation on drug metabolism and its consequences for precision medicine therapies. This approach involved a literature review of various scientific articles discussing pharmacogenomics, CYP450 enzymes, and their clinical applications. The findings indicate that CYP450 enzymes are crucial in drug metabolism, especially during phase I reactions, such as oxidation, and their activity is heavily influenced by genetic polymorphisms, including those in CYP2C19. These genetic differences lead to variations in the ability of individuals to activate or eliminate drugs, thereby affecting the effectiveness of therapy and the likelihood of side effects. In addition to genetic factors, drug interactions, environmental influences, and the microbiome also play a role in drug response. For instance, genetic variation in the use of clopidogrel can result in therapeutic failure or a heightened risk of clinical events. Ultimately, integrating genomic data from the HGP with CYP450 enzyme profiles provides a vital basis for implementing precision medicine, allowing for more accurate drug and dosage selection, thereby enhancing therapeutic effectiveness and reducing the risk of side effects in patients.
Downloads
References
[1] E. A. Ashley, “The Precision Medicine Initiative,” JAMA, vol. 313, no. 21, p. 2119, Jun. 2015, doi: 10.1001/jama.2015.3595.
[2] M. V. Relling and W. E. Evans, “Pharmacogenomics in the clinic,” Nature, vol. 526, no. 7573, pp. 343–350, Oct. 2015, doi: 10.1038/nature15817.
[3] K. E. Caudle et al., “Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC),” Genetics in Medicine, vol. 19, no. 2, pp. 215–223, Feb. 2017, doi: 10.1038/gim.2016.87.
[4] D. L. Hertz et al., “Recommendations for pharmacogenetic testing in clinical practice guidelines in the US,” American Journal of Health-System Pharmacy, vol. 81, no. 16, pp. 672–683, Aug. 2024, doi: 10.1093/ajhp/zxae110.
[5] K. E. Caudle et al., “Standardizing CYP2D6 Genotype to Phenotype Translation: Consensus Recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group,” Clin. Transl. Sci., vol. 13, no. 1, pp. 116–124, Jan. 2020, doi: 10.1111/cts.12692.
[6] D. M. Roden, R. A. Wilke, H. K. Kroemer, and C. M. Stein, “Pharmacogenomics: The genetics of variable drug responses,” Circulation, vol. 123, no. 15, pp. 1661–1670, Apr. 2011, doi: 10.1161/CIRCULATIONAHA.109.914820.
[7] M. Zhao et al., “Cytochrome P450 Enzymes and Drug Metabolism in Humans,” Int. J. Mol. Sci., vol. 22, no. 23, p. 12808, Nov. 2021, doi: 10.3390/ijms222312808.
[8] R. Hassan et al., “Drug response in association with pharmacogenomics and pharmacomicrobiomics: towards a better personalized medicine,” Brief. Bioinform., vol. 22, no. 4, Jul. 2021, doi: 10.1093/bib/bbaa292.
[9] M. Deodhar et al., “Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice,” Pharmaceutics, vol. 12, no. 9, p. 846, Sep. 2020, doi: 10.3390/pharmaceutics12090846.
[10] J. Oates and D. Lopez, “Pharmacogenetics: An Important Part of Drug Development with A Focus on Its Application,” Int. J. Biomed. Investig., vol. 1, no. 2, pp. 1–16, Jun. 2018, doi: 10.31531/2581-4745.1000111.
[11] S.-A. Brown and N. Pereira, “Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine,” J. Pers. Med., vol. 8, no. 1, p. 8, Jan. 2018, doi: 10.3390/jpm8010008.
[12] H. Zwart, “Human Genome Project: History and Assessment,” in International Encyclopedia of the Social & Behavioral Sciences: Second Edition, Elsevier Inc., 2015, pp. 311–317. doi: 10.1016/B978-0-08-097086-8.82036-X.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Anastasya Esther Fiorelina Siahaan, Juniza Firdha Suparningtyas, Isti Faiza Sakinah, Khairani Tosuli, Ayla Azzura, Anastasya Esther Fiorelina Siahaan, Sabrina, Nanda Febriani, Maria Beatrix Ose Purek, Kaylila Aileen, Salwa Salsa Billa, Tasya Falda Puteri (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

