Comprehensive Review of Clinically Relevant Drug-Gene Interactions in Pharmacy Practice: A UKBB Data Guide for Providers
Main Article Content
Keywords
Pharmacogenomics, pharmacy practice, drug responece, Genetic tests, Drug-gene interactions, Healthcare institutions, Drug safety and efficacy, KBB prescribing data, commonly prescribed drugs
Abstract
The translation of pharmacogenomic insights into clinical practice faces a significant barrier stemming from the lack of knowledge and guidance within healthcare institutions for prioritizing genetic tests and drug-gene interactions. To address this critical challenge, we provide a single, simple, user-friendly, and comprehensive electronic database of all important drug-gene interactions (n =421) with summaries of clinical recommendations per association as classified into our simple triple classification system (A, B, or C) depending on their clinical relevance (https://c1abo933.caspio.com/dp/ d81f70009de6d5055c2a44a5a970 ). The database can be looked at as a roadmap for healthcare providers in health care settings facilitating practicing pharmacogenomics in their institutions. To present how the database can be effectively utilized, we utilized the longitudinal prescribing data from across different UK health care institutions (the UKBB dataset) for ~ 230,000 participants to identify the most frequently prescribed drugs in the UK and linking them with our database. This enabled us to uncover the most frequently used drugs in the UK which have genotype-guided clinical recommendations. Then, we show, using a scoring approach, which specific drug-gene interactions should be prioritized over others in any given health care institution using an example from our analyzed UKBB data. Generally, we propose the genetic testing of 114 key genes covering all significant drug-gene associations. However, we specifically recommend prioritization of genetic testing for CYP2D6 and G6PD genes, acknowledging that they are involved in ~ 30% of all important drug-gene associations. This paper holds profound promise for advancing clinical practice and patient care.
References
prescribing to prevent gene-drug-related deaths: A decision-analytic model. Frontiers in Pharmacology. 2022;13. doi:10.3389/fphar.2022.918493
2. Hockings JK, Pasternak AL, Erwin AL, Mason NT, Eng C, Hicks JK. Pharmacogenomics: An evolving clinical tool for precision
medicine. Cleveland Clinic Journal of Medicine. 2020;87(2):91–9. doi:10.3949/ccjm.87a.19073
3. Cacabelos R, Cacabelos N, Carril JC. The role of Pharmacogenomics in adverse drug reactions. Expert Review of Clinical
Pharmacology. 2019;12(5):407–42. doi:10.1080/17512433.2019.1597706
4. Verbelen M, Weale ME, Lewis CM. Cost-effectiveness of pharmacogenetic-guided treatment: Are we there yet? The
Pharmacogenomics Journal. 2017;17(5):395–402. doi:10.1038/tpj.2017.21
5. Berm EJ, Looff M de, Wilffert B, Boersma C, Annemans L, Vegter S, et al. Economic evaluations of Pharmacogenetic and
pharmacogenomic screening tests: A systematic review. Second update of the literature. PLOS ONE. 2016;11(1). doi:10.1371/journal.pone.0146262
6. Rahawi, S. et al. (2020) ‘Knowledge and attitudes on pharmacogenetics among pediatricians’, Journal of Human Genetics,
65(5), pp. 437–444. doi:10.1038/s10038-020-0723-0.
7. Raccor, B.S. et al. (2020) ‘Assessment and clinical utility of pharmacogenomics by Healthcare Practitioners in North Carolina’,
Pharmacogenomics, 22(1), pp. 13–25. doi:10.2217/pgs-2020-0108.
8. Maruf, A.A. et al. (2024) ‘Knowledge and perceptions of pharmacogenomics among pharmacists in Manitoba, Canada’,
Pharmacogenomics, 25(4), pp. 175–186. doi:10.2217/pgs-2024-0013.
9. Petit, C. et al. (2020) ‘Are pharmacists from the province of Quebec ready to integrate pharmacogenetics into their practice’, Pharmacogenomics, 21(4), pp. 247–256. doi:10.2217/pgs-2019-0144.
10. Edris, A. et al. (2020) ‘Pharmacogenetics in clinical practice: Current level of knowledge among Flemish physicians and
pharmacists’, The Pharmacogenomics Journal, 21(1), pp. 78–84. doi:10.1038/s41397-020-00180-x.
11. Jameson, A. et al. (2021) ‘What are the barriers and enablers to the implementation of pharmacogenetic testing in mental
health care settings?’, Frontiers in Genetics, 12. doi:10.3389/fgene.2021.740216.
12. Pop, C. et al. (2022) ‘Nation-wide survey assessing the knowledge and attitudes of Romanian pharmacists concerning pharmacogenetics’, Frontiers in Pharmacology, 13. doi:10.3389/fphar.2022.952562.
13. Verdez, S. et al. (2024) ‘Experience and expectations of pharmacogenetic tests in France’, Therapies, 79(3), pp. 341–349. doi:10.1016/j.therap.2023.07.002.
14. Karuna, N. et al. (2020) ‘Knowledge, attitude, and practice towards pharmacogenomics among hospital pharmacists in
Thailand’, Pharmacogenetics and Genomics, 30(4), pp. 73–80. doi:10.1097/fpc.0000000000000399.
15. Tsuji, D. et al. (2021) ‘Results of a nationwide survey of Japanese pharmacists regarding the application of pharmacogenomic
testing in Precision Medicine’, Journal of Clinical Pharmacy and Therapeutics, 46(3), pp. 649–657. doi:10.1111/jcpt.13367.
16. Nie, X. et al. (2022) ‘Clinical pharmacists’ knowledge of and attitudes toward pharmacogenomic testing in China’, Journal of Personalized Medicine, 12(8), p. 1348. doi:10.3390/jpm12081348.
17. Alzoubi, A. et al. (2020) ‘Knowledge, attitude, future expectations and perceived barriers of medical students and physicians regarding pharmacogenomics in Jordan’, International Journal of Clinical Practice, 75(1). doi:10.1111/ijcp.13658.
18. Rahma, A.T. et al. (2020) ‘Knowledge, attitudes, and perceived barriers toward genetic testing and pharmacogenomics among healthcare workers in the United Arab Emirates: A cross-sectional study’, Journal of Personalized Medicine, 10(4), p. 216. doi:10.3390/jpm10040216.
19. Albitar, L. and Alchamat, G.A. (2021) ‘Pharmacogenetics: Knowledge assessment amongst Syrian pharmacists and physicians’, BMC Health Services Research, 21(1). doi:10.1186/s12913-021-07040-9.
20. Alhaddad, Z.A., AlMousa, H.A. and Younis, N.S. (2022) ‘Pharmacists’ knowledge, and insights in implementing pharmacogenomics in Saudi Arabia’, International Journal of Environmental Research and Public Health, 19(16), p. 10073. doi:10.3390/ijerph191610073.
21. Algahtani, M. (2020) ‘
knowledge, perception, and application of pharmacogenomics among hospital pharmacists in Saudi arabia
’, Risk Management and Healthcare Policy, Volume 13, pp. 1279–1291. doi:10.2147/rmhp.s267492.22. Bagher, A.M. et al. (2021) ‘Knowledge, perception, and confidence of hospital pharmacists toward pharmacogenetics in Jeddah, Kingdom of Saudi Arabia’, Saudi Pharmaceutical Journal, 29(1), pp. 53–58. doi:10.1016/j.jsps.2020.12.006.
23. Nagy, M. et al. (2020) ‘Assessment of healthcare professionals’ knowledge, attitudes, and perceived challenges of clinical
pharmacogenetic testing in Egypt’, Personalized Medicine, 17(4), pp. 251–260. doi:10.2217/pme-2019-0163.
24. Mufwambi, W. et al. (2021) ‘Healthcare professionals’ knowledge of pharmacogenetics and attitudes towards antimicrobial utilization in Zambia: Implications for a precision medicine approach to reducing antimicrobial resistance’, Frontiers in Pharmacology, 11. doi:10.3389/fphar.2020.551522.
25. Abubakar, U. et al. (2022) ‘Knowledge, attitude and perception of community pharmacists towards Pharmacogenomics Services in Northern Nigeria: A cross-sectional study’, Journal of Pharmaceutical Policy and Practice, 15(1). doi:10.1186/s40545-022-00435-x.
26. Pearce, A. et al. (2022) ‘Pharmacogenomic testing: Perception of clinical utility, enablers and barriers to adoption in Australian hospitals’, Internal Medicine Journal, 52(7), pp. 1135–1143. doi:10.1111/imj.15719.
27. PharmGKB P [Internet]. 2023 [cited 2023 Oct 22]. Available from: https://www.pharmgkb.org/
28. Nkhoma ET, Poole C, Vannappagari V, Hall SA, Beutler E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis. Blood Cells, Molecules, and Diseases. 2009;42(3):267–78. doi:10.1016/j.bcmd.2008.12.005
29. Koopmans AB, Braakman MH, Vinkers DJ, Hoek HW, van Harten PN. Meta-analysis of probability estimates of worldwide
variation of CYP2D6 and CYP2C19. Translational Psychiatry. 2021;11(1). doi:10.1038/s41398-020-01129-1
30. Biswas M. Global distribution of CYP2C19 risk phenotypes affecting safety and effectiveness of medications. The Pharmacogenomics Journal. 2020;21(2):190–9. doi:10.1038/s41397-020-00196-3
31. Skryabin VY, Zastrozhin M, Torrado M, Grishina E, Ryzhikova K, Shipitsyn V, et al. Effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam in patients with alcohol withdrawal syndrome. Psychiatric Genetics. 2022;32(2):67–73. doi:10.1097/ypg.0000000000000306
32. Zubiaur P, Figueiredo-Tor L, Villapalos-García G, Soria-Chacartegui P, Navares-Gómez M, Novalbos J, et al. Association between CYP2C19 and CYP2B6 phenotypes and the pharmacokinetics and safety of diazepam. Biomedicine & Pharmacotherapy. 2022;155:113747. doi:10.1016/j.biopha.2022.113747
33. Malki MA, Pearson ER. Drug–drug–gene interactions and adverse drug reactions. The Pharmacogenomics Journal. 2019;20(3):355–66. doi:10.1038/s41397-019-0122-0
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.