Skip to main content
SpringerLink
Log in
Book cover

Pharmacogenomics pp 3–22Cite as

Pharmacogenomics: Historical Perspective and Current Status

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1015))

Abstract

Pharmacogenomics and its predecessor pharmacogenetics study the contribution of genetic factors to the interindividual variability in drug efficacy and safety. One of the major goals of pharmacogenomics is to tailor drugs to individuals based on their genetic makeup and molecular profile. From early findings in the 1950s uncovering inherited deficiencies in drug metabolism that explained drug-related adverse events, to nowadays genome-wide approaches assessing genetic variation in multiple genes, pharmacogenomics has come a long way. The evolution of pharmacogenomics has paralleled the evolution of genotyping technologies, the completion of the human genome sequencing and the HapMap project. Despite these advances, the implementation of pharmacogenomics in clinical practice has yet been limited. Here we present an overview of the history and current applications of pharmacogenomics in patient selection, dosing, and drug development with illustrative examples of these categories. Some of the challenges in the field and future perspectives are also presented.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Offit K (2011) Personalized medicine: new genomics, old lessons. Hum Genet 130(1): 3–14

    Article  PubMed  Google Scholar 

  2. Weinshilboum R, Wang L (2004) Pharmacogenomics: bench to bedside. Nat Rev Drug Discov 3(9):739–748

    Article  PubMed  CAS  Google Scholar 

  3. Kalow W et al (1998) Hypothesis: comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. Pharmacogenetics 8(4):283–289

    Article  PubMed  CAS  Google Scholar 

  4. Evans WE, McLeod HL (2003) Pharmacogenomics—drug disposition, drug targets, and side effects. N Engl J Med 348(6):538–549

    Article  PubMed  CAS  Google Scholar 

  5. Roden DM et al (2006) Pharmacogenomics: challenges and opportunities. Ann Intern Med 145(10):749–757

    Article  PubMed  Google Scholar 

  6. Camilleri M, Saito YA (2008) Pharmacogenomics in gastrointestinal disorders. Methods Mol Biol 448:395–412

    Article  PubMed  CAS  Google Scholar 

  7. Kirk RJ et al (2008) Implications of pharmacogenomics for drug development. Exp Biol Med (Maywood) 233(12):1484–1497

    Article  CAS  Google Scholar 

  8. McLeod HL, Evans WE (2001) Pharmacogenomics: unlocking the human genome for better drug therapy. Annu Rev Pharmacol Toxicol 41:101–121

    Article  PubMed  CAS  Google Scholar 

  9. Watters JW, McLeod HL (2003) Cancer pharmacogenomics: current and future applications. Biochim Biophys Acta 1603(2):99–111

    PubMed  CAS  Google Scholar 

  10. Hudson KL (2011) Genomics, health care, and society. N Engl J Med 365(11): 1033–1041

    Article  PubMed  CAS  Google Scholar 

  11. Snyder LH (1932) Studies in human inheritance. IX. The inheritance of taste deficiency in man. Ohio J Sci 32:436–468

    Google Scholar 

  12. Kim UK et al (2003) Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299(5610):1221–1225

    Article  PubMed  CAS  Google Scholar 

  13. Motulsky AG (1957) Drug reactions enzymes, and biochemical genetics. J Am Med Assoc 165(7):835–837

    Article  PubMed  CAS  Google Scholar 

  14. Vogel F (1959) Moderne probleme der humangenetik. Ergebn Inn Med Kinderheilkd 12:52–125

    Article  Google Scholar 

  15. Nebert DW et al (2008) From human genetics and genomics to pharmacogenetics and pharmacogenomics: past lessons, future directions. Drug Metab Rev 40(2):187–224

    Article  PubMed  CAS  Google Scholar 

  16. Ma Q, Lu AY (2011) Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 63(2):437–459

    Article  PubMed  CAS  Google Scholar 

  17. Gonzalez FJ et al (1988) Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 331(6155):442–446

    Article  PubMed  CAS  Google Scholar 

  18. Blum M et al (1990) Human arylamine N-acetyltransferase genes - isolation, chromosomal localization, and functional expression. DNA Cell Biol 9(3):193–203

    Article  PubMed  CAS  Google Scholar 

  19. Krynetski EY et al (1995) A single-point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc Natl Acad Sci USA 92(4):949–953

    Article  PubMed  CAS  Google Scholar 

  20. Vesell ES (1989) Pharmacogenetic perspectives gained from twin and family studies. Pharmacol Ther 41(3):535–552

    Article  PubMed  CAS  Google Scholar 

  21. Shin J et al (2009) Pharmacogenetics: from discovery to patient care. Am J Health Syst Pharm 66(7):625–637

    Article  PubMed  CAS  Google Scholar 

  22. Roden DM et al (2011) Pharmacogenomics: the genetics of variable drug responses. Circulation 123(15):1661–1670

    Article  PubMed  Google Scholar 

  23. Evans WE, Relling MV (1999) Relling, Pharmacogenomics: translating functional genomics into rational therapeutics. Science, 286(5439):487–491

    Article  PubMed  Google Scholar 

  24. Belle DJ, Singh H (2008) Genetic factors in drug metabolism. Am Fam Physician 77(11): 1553–1560

    PubMed  Google Scholar 

  25. Gaedigk A et al (2008) The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther 83(2):234–242

    Article  PubMed  CAS  Google Scholar 

  26. Desta Z et al (2002) Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 41(12):913–958

    Article  PubMed  Google Scholar 

  27. Mini E, Nobili S (2009) Pharmacogenetics: implementing personalized medicine. Clin Cases Miner Bone Metab 6(1):17–24

    PubMed  Google Scholar 

  28. Venter JC et al (2001) The sequence of the human genome. Science 291(5507): 1304–1351

    Article  PubMed  CAS  Google Scholar 

  29. Lander ES et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921

    Article  PubMed  CAS  Google Scholar 

  30. den Dunnen JT, Antonarakis SE (2001) Nomenclature for the description of human sequence variations. Hum Genet 109(1): 121–124

    Article  Google Scholar 

  31. Kacevska M et al (2011) Perspectives on epigenetics and its relevance to adverse drug reactions. Clin Pharmacol Ther 89(6): 902–907

    Article  PubMed  CAS  Google Scholar 

  32. O’Donnell PH, Dolan ME (2009) Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy. Clin Cancer Res 15(15):4806–4814

    Article  PubMed  Google Scholar 

  33. Lee W et al (2005) Cancer pharmacogenomics: powerful tools in cancer chemotherapy and drug development. Oncologist 10(2):104–111

    Article  PubMed  CAS  Google Scholar 

  34. Judson R et al (2000) The predictive power of haplotypes in clinical response. Pharmacogenomics 1(1):15–26

    Article  PubMed  CAS  Google Scholar 

  35. Fujiwara Y, Minami H (2010) An overview of the recent progress in irinotecan pharmacogenetics. Pharmacogenomics 11(3):391–406

    Article  PubMed  CAS  Google Scholar 

  36. Becquemont L (2009) Pharmacogenomics of adverse drug reactions: practical applications and perspectives. Pharmacogenomics 10(6): 961–969

    Article  PubMed  CAS  Google Scholar 

  37. Wu X et al (2009) Strategies to identify pharmacogenomic biomarkers: candidate gene, pathway-based, and genome-wide approaches. In: Innocenti F (ed) Genomics and pharmacogenomics in anticancer drug development and clinical response. Humana Press, Totowa NJ, pp 353–370

    Google Scholar 

  38. Feero WG et al (2010) Genomic medicine—an updated primer. N Engl J Med 362(21):2001–2011

    Article  PubMed  CAS  Google Scholar 

  39. Metzker ML (2010) Sequencing technologies—the next generation. Nat Rev Genet 11(1):31–46

    Article  PubMed  CAS  Google Scholar 

  40. Wilke RA et al (2007) Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges. Nat Rev Drug Discov 6(11):904–916

    Article  PubMed  CAS  Google Scholar 

  41. Andrade RJ et al (2009) Drug-induced liver injury: insights from genetic studies. Pharmacogenomics 10(9):1467–1487

    Article  PubMed  CAS  Google Scholar 

  42. Huang YS (2010) Tailored drug therapy for mitigating drug-induced liver injury: is this the era of genetic screening? Pers Med 7(1):5–8

    Article  Google Scholar 

  43. Wang L et al (2011) Genomics and drug response. N Engl J Med 364(12):1144–1153

    Article  PubMed  CAS  Google Scholar 

  44. Daly AK et al (2009) HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 41(7):816–819

    Article  PubMed  CAS  Google Scholar 

  45. Kindmark A et al (2008) Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J 8(3):186–195

    Article  PubMed  CAS  Google Scholar 

  46. Singer JB et al (2010) A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet 42(8):711–714

    Article  PubMed  CAS  Google Scholar 

  47. Tujios S, Fontana RJ (2011) Mechanisms of drug-induced liver injury: from bedside to bench. Nat Rev Gastroenterol Hepatol 8(4): 202–211

    Article  PubMed  CAS  Google Scholar 

  48. Pirmohamed M (2010) Pharmacogenetics of idiosyncratic adverse drug reactions. Handb Exp Pharmacol 196:477–491

    Article  PubMed  CAS  Google Scholar 

  49. Becquemont L (2010) HLA: a pharmacogenomics success story. Pharmacogenomics 11(3):277–281

    Article  PubMed  Google Scholar 

  50. Mallal S et al (2008) HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358(6):568–579

    Article  PubMed  Google Scholar 

  51. Hung SI et al (2006) Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 16(4):297–306

    Article  PubMed  CAS  Google Scholar 

  52. TEGRETOL(Carbamazepine) Labeling [Online].http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/016608s100s102s.s.,018927s041s042,020234s031s033lbl.pdf. Accessed 31 Oct 2011

  53. McCormack M et al (2011) HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364(12):1134–1143

    Article  PubMed  CAS  Google Scholar 

  54. Ozeki T et al (2011) Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet 20(5):1034–1041

    Article  PubMed  CAS  Google Scholar 

  55. Somkrua R et al (2011) Association of HLA-B*5801 allele and Allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC Med Genet 12(1):118

    Article  PubMed  CAS  Google Scholar 

  56. Niemi M (2010) Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 87(1):130–133

    Article  PubMed  CAS  Google Scholar 

  57. Link E et al (2008) SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med 359(8):789–799

    Article  PubMed  CAS  Google Scholar 

  58. Walko CM, McLeod H (2009) Pharmacogenomic progress in individualized dosing of key drugs for cancer patients. Nat Clin Pract Oncol 6(3):153–162

    Article  PubMed  CAS  Google Scholar 

  59. Innocenti F, Ratain MJ (2006) Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotyping. Pharmacogenomics 7(8):1211–1221

    Article  PubMed  CAS  Google Scholar 

  60. Wilke RA, Dolan ME (2011) Genetics and variable drug response. JAMA 306(3):306–307

    Article  PubMed  CAS  Google Scholar 

  61. Carlquist JF, Anderson JL (2011) Pharmacogenetic mechanisms underlying unanticipated drug responses. Discov Med 11(60):469–478

    PubMed  Google Scholar 

  62. Lovly CM, Carbone DP (2011) Lung cancer in 2010: one size does not fit all. Nat Rev Clin Oncol 8(2):68–70

    Article  PubMed  CAS  Google Scholar 

  63. Biankin AV, Hudson TJ (2011) Somatic variation and cancer: therapies lost in the mix. Hum Genet 130(1):79–91

    Article  PubMed  Google Scholar 

  64. Chapman PB et al (2011) Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364(26): 2507–2516

    Article  PubMed  CAS  Google Scholar 

  65. Shaw AT et al (2011) Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 12(11):1004–1012

    Article  PubMed  CAS  Google Scholar 

  66. Hutchinson L (2010) Targeted therapies: activated PI3K/AKT confers resistance to trastuzumab but not lapatinib. Nat Rev Clin Oncol 7(8):424

    Article  PubMed  Google Scholar 

  67. Ellis LM, Hicklin DJ (2009) Resistance to targeted therapies: refining anticancer therapy in the era of molecular oncology. Clin Cancer Res 15(24):7471–7478

    Article  PubMed  CAS  Google Scholar 

  68. PLAVIX (Clopidogrel) Labeling [Online]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020839s051lbl.pdf. Accessed 28 Aug

  69. Mega JL et al (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360(4):354–362

    Article  PubMed  CAS  Google Scholar 

  70. Mega JL et al (2010) Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304(16):1821–1830

    Article  PubMed  CAS  Google Scholar 

  71. Scott SA et al (2011) Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and Clopidogrel therapy. Clin Pharmacol Ther 90(2):328–332

    Article  PubMed  CAS  Google Scholar 

  72. Daly AK, King BP (2003) Pharmacogenetics of oral anticoagulants. Pharmacogenetics 13(5):247–252

    Article  PubMed  CAS  Google Scholar 

  73. Kim MJ et al (2009) A regulatory science perspective on warfarin therapy: a pharmacogenetic opportunity. J Clin Pharmacol 49(2):138–146

    Article  PubMed  CAS  Google Scholar 

  74. Scordo MG et al (2002) Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin Pharmacol Ther 72(6):702–710

    Article  PubMed  CAS  Google Scholar 

  75. Sconce EA et al (2005) The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 106(7):2329–2333

    Article  PubMed  CAS  Google Scholar 

  76. Marsh S et al (2006) Population variation in VKORC1 haplotype structure. J Thromb Haemost 4(2):473–474

    Article  PubMed  CAS  Google Scholar 

  77. Yuan HY et al (2005) A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 14(13):1745–1751

    Article  PubMed  CAS  Google Scholar 

  78. Gage BF, Lesko LJ (2008) Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues. J Thromb Thrombolysis 25(1):45–51

    Article  PubMed  CAS  Google Scholar 

  79. Caraco Y et al (2008) CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin Pharmacol Ther 83(3):460–470

    Article  PubMed  CAS  Google Scholar 

  80. Gage BF et al (2008) Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin Pharmacol Ther 84(3): 326–331

    Article  PubMed  CAS  Google Scholar 

  81. Lenzini P et al (2010) Integration of genetic, clinical, and INR data to refine warfarin dosing. Clin Pharmacol Ther 87(5):572–578

    Article  PubMed  CAS  Google Scholar 

  82. COUMADIN (Warfarin) prescribing information. [Online]. www.accessdata.fda.gov/drugsatfda_docs/label/2010/009218s108lbl.pdf. Accessed 28 Aug

  83. Tetrabenazine Clinical Pharmacology Review. [Online]. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021894s000TOC.cfm. Accessed 28 Aug

  84. XENAZINE (Tetrabenazine) Labeling [Online]. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021894s004lbl.pdf. Accessed 28 Aug

  85. Stingl Kirchheiner JC, Brockmoller J (2011) Why, when, and how should pharmacogenetics be applied in clinical studies? Current and future approaches to study designs. Clin Pharmacol Ther 89(2):198–209

    Article  PubMed  CAS  Google Scholar 

  86. Zineh I, Pacanowski MA (2011) Pharmacogenomics in the assessment of therapeutic risks versus benefits: inside the United states food and drug administration. Pharmacotherapy 31(8):729–735

    Article  PubMed  CAS  Google Scholar 

  87. Diamandis M et al (2010) Personalized medicine: marking a new epoch in cancer patient management. Mol Cancer Res 8(9):1175–1187

    Article  PubMed  CAS  Google Scholar 

  88. Houle D et al (2010) Phenomics: the next challenge. Nat Rev Genet 11(12):855–866

    Article  PubMed  CAS  Google Scholar 

  89. Pirmohamed M et al (2011) The phenotype standardization project: improving pharmacogenetic studies of serious adverse drug reactions. Clin Pharmacol Ther 89(6): 784–785

    Article  PubMed  CAS  Google Scholar 

  90. Lanktree MB et al (2010) Phenomics: expanding the role of clinical evaluation in genomic studies. J Investig Med 58(5): 700–706

    PubMed  CAS  Google Scholar 

  91. Tracy RP (2008) ‘Deep phenotyping’: characterizing populations in the era of genomics and systems biology. Curr Opin Lipidol 19(2):151–157

    Article  PubMed  CAS  Google Scholar 

  92. Carson PE et al (1956) Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124(3220):484–485

    Article  PubMed  CAS  Google Scholar 

  93. Kalow W (1956) Familial incidence of low pseudocholinesterase level. Lancet 271:576–577

    Article  Google Scholar 

  94. Harris HW et al (1958) Comparison of isoniazid concentrations in the blood of people of Japanese and European descent; therapeutic and genetic implications. Am Rev Tuberc 78(6):944–948

    PubMed  CAS  Google Scholar 

  95. Evans DA et al (1960) Genetic control of isoniazid metabolism in man. Br Med J 2(5197):485–491

    Article  PubMed  CAS  Google Scholar 

  96. Mahgoub A et al (1977) Polymorphic hydroxylation of Debrisoquine in man. Lancet 2(8038):584–586

    Article  PubMed  CAS  Google Scholar 

  97. Eichelbaum M et al (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16(3):183–187

    Article  PubMed  CAS  Google Scholar 

  98. Weinshilboum RM, Sladek SL (1980) Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 32(5):651–662

    PubMed  CAS  Google Scholar 

  99. Ge D et al (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461(7262):399–401

    Article  PubMed  CAS  Google Scholar 

  100. Eichler HG et al (2011) Bridging the efficacy-effectiveness gap: a regulator’s perspective on addressing variability of drug response. Nat Rev Drug Discov 10(7):495–506

    Article  PubMed  CAS  Google Scholar 

  101. Bertilsson L et al (2002) Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 53(2):111–122

    Article  PubMed  CAS  Google Scholar 

  102. Janne PA et al (2009) Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat Rev Drug Discov 8(9): 709–723

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors acknowledge Dr. Issam Zineh for critical review of the manuscript.

Author information

Authors and Affiliations

  1. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, USA

    Rosane Charlab & Lei Zhang

Authors
  1. Rosane Charlab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute for Pharmacogenomics, and Individualized Therapy, University of North Carolina, Mason Farm Rd. 120, Chapel Hill, 27599-7361, North Carolina, USA

    Federico Innocenti

  2. , Dept. of Clinical Chemistry (AKC), Erasmus MC, Gravendijkwal 230, Rotterdam, 3015, Netherlands

    Ron H.N. van Schaik

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Charlab, R., Zhang, L. (2013). Pharmacogenomics: Historical Perspective and Current Status. In: Innocenti, F., van Schaik, R. (eds) Pharmacogenomics. Methods in Molecular Biology, vol 1015. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-435-7_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-435-7_1

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-434-0

  • Online ISBN: 978-1-62703-435-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation