AccScience Publishing / EJMO / Volume 3 / Issue 2 / DOI: 10.14744/ejmo.2019.52584
REVIEW

Understanding Clinical Pharmacogenomics: A Descriptive Review

Jesse Ramey1 Prashanth Manjunatha Reddy1 Narendra Sai Varma Datla1 Shivaprakash Bayapalli1 Yogesh Acharya1
Show Less
1 Department of Basic Sciences, Avalon University School of Medicine, Willemstad, Curacao
EJMO 2019, 3(2), 92–100; https://doi.org/10.14744/ejmo.2019.52584
Submitted: 6 February 2019 | Accepted: 15 March 2019 | Published: 22 March 2019
© 2019 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Pharmacogenomics (PGx) is the study of the correlation between an individual’s genome and their response to specific medications. While different individuals respond differently to drugs, it has only been since the documentation of the human genome in 2003 that researchers have been able to make a tighter genetic connection with their metabolism. This study explores the current state of the PGx as of 2019 with an emphasis on its clinical usefulness. We analyzed data from the Food and Drug Administration (FDA), the Clinical Pharmacogenetics Implementation Consortium (CPIC) and PharmGKB, three key organizations that support pharmacogenomics in the US. A supported literature review was performed from PubMed and ClinCalc. We identified 27 drug-biomarker pairs on the highest ratings of confidence based on FDA, CPIC, and PharmGKB and chose 9 exemplary drugs to tabulate the association study (GWAS), PharmGKB dosing and FDA PGx actionability.

Keywords
Clinical implementation
description
pharmacogenomics
pharmacogenetics
Conflict of interest
None declared.
References

What was the Human Genome Project and why has it been important? Genetics Home Reference. July 3, 2018. Available at: https://ghr.nlm.nih.gov/primer/hgp/description. Accessed March 15, 2019.

2. What We Do. FDA. Available at: https://www.fda.gov/AboutFDA/WhatWeDo/default.htm. Accessed March 15, 2019.

3. CPIC. What is CPIC? Available at: https://cpicpgx.org/. Accessed March 15, 2019.

4. Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn F, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2012;92:414–7. [CrossRef]

5. Genome-Wide Association Studies. National Human Genome Research Institute (NHGRI). 2018. Available at: https://www. genome.gov/20019523/genomewide-association-studiesfact-sheet/. Accessed March 15, 2019.

6. Clinical tools and calculators for medical professionals – ClinCalc. Available from: http://clincalc.com/. Accessed March 15, 2019.

7. About the HGNC. Available from: https://www.genenames. org/about/overview. Accessed March 15, 2019.

8. HLA Nomenclature. Nomenclature for Factors of the HLA System. Available at http://hla.alleles.org/nomenclature/index. html. Accessed March 15, 2019.

9. Single Nucleotide Polymorphisms (SNPs). National Human Genome Research Institute (NHGRI). Available at: https:// www.genome.gov/glossary/index.cfm?id=185. Accessed March 15, 2019.

10. Whalen K, Finkel R, Panavelil TA. Pharmacology. 6th edition.Philadelphia: Wolters Kluwer; 2015.

11. Crews KR, Gaedigk A, Dunnenberger HM, Leeder JS, Klein TE, Caudle KE, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 2014;95:376–82. [CrossRef]

12. Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther 2011;91:321–6. [CrossRef]

13. Johnson JA, Caudle KE, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for PharmacogeneticsGuided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther 2017;102:397–404. [CrossRef]

14. Daneshi N, Holliday E, Hancock S, Schneider JJ, Scott RJ, Attia J, et al. Prevalence of clinically actionable genotypes and medication exposure of older adults in the community. Pharmgenomics Pers Med 2017;10:17–27. [CrossRef]

15. Scott SA, Sangkuhl K, Stein CM, Hulot JS, Mega JL, Roden DM, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther 2013;94:317–23. [CrossRef]

16. Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011;89:387–91.

17. Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther 2015;98:19–24. [CrossRef]

18. Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S, Lee MT, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther 2014;96:542–8. [CrossRef]

19. Leckband SG, Kelsoe JR, Dunnenberger HM, George AL Jr, Tran E, Berger R, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther 2013;94:324–8. [CrossRef]

20. Martin MA, Klein TE, Dong BJ, Pirmohamed M, Haas DW, Kroetz DL; Clinical Pharmacogenetics Implementation Consortium. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther 2012;91:734–8. [CrossRef]

21. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358:568–79. [CrossRef]

22. Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, et al. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther 2014;96:423–8.

23. Dailymed. NIH. Available at: https://dailymed.nlm.nih.gov/ dailymed/index.cfm. Accessed March 15, 2019.

24. Linan MK, Sottara D, Freimuth RR. Creating Shareable Clini-cal Decision Support Rules for a Pharmacogenomics Clinical Guideline Using Structured Knowledge Representation. AMIA Annu Symp Proc 2015;2015:1985–94.

25. Schroeder MO. Death by prescription.US News World Report. Available at: https://health.usnews.com/health-news/patientadvice/articles/2016-09-27/the-danger-in-taking-prescribedmedications. Accessed March 15, 2019.

26. Johnson JA. Pharmacogenetics in clinical practice: how far have we come and where are we going? Pharmacogenomics 2013;14:835–43. [CrossRef]

27. O'Donnell PH, Danahey K, Ratain MJ. The Outlier in All of Us:Why Implementing Pharmacogenomics Could Matter for Ev-eryone. Clin Pharmacol Ther 2016;99:401–4. [CrossRef]

28. Alessandrini M, Chaudhry M, Dodgen TM, Pepper MS. Pharmacogenomics and Global Precision Medicine in the Context of Adverse Drug Reactions: Top 10 Opportunities and Challenges for the Next Decade. OMICS 2016;20:593–603.

29. Mooney SD. Progress towards the integration of pharmacogenomics in practice. Hum Genet 2014;134:459–65. [CrossRef]

30. Johnson SG. Leading clinical pharmacogenomics implementation: Advancing pharmacy practice. 2015. Am J Health Syst Pharm 2015;72:1324–8. [CrossRef]

31. Samwald M, Miñarro Giménez JA, Boyce RD, Freimuth RR, Adlassnig KP, Dumontier M. Pharmacogenomic knowledge representation, reasoning and genome-based clinical decision support based on OWL 2 DL ontologies. BMC Med Inform Decis Mak 2015;15:12. [CrossRef]

32. Owusu Obeng A, Fei K, Levy KD, Elsey AR, Pollin TI, Ramirez AH, et al. Physician-Reported Benefits and Barriers to Clinical Implementation of Genomic Medicine: A Multi-Site IGNITENetwork Survey. J Pers Med 2018;8. pii:24. [CrossRef]

Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing