Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Science and Society
  • Published:

The impact of pharmacogenetics and pharmacogenomics on drug discovery

Nature Reviews Drug Discovery volume 1, pages 463–469 (2002)Cite this article

Abstract

It is widely perceived at present that pharmacogenetics and pharmacogenomics are about to revolutionize the face of medicine. In a more realistic assessment, the implementation of molecular genetics and biology will provide us with better ways to treat illnesses, and has already begun to do so in an incremental and evolutionary fashion. However, it is unlikely to change fundamentally the direction of medical progress. Advances are most likely to be made in the area of pharmacodynamics, as we learn to differentiate broader conventional clinical diagnoses into separate molecular subtypes.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Two models for pharmacogenetics that are based on pharmacodynamics: aetiology-related and palliation-related mechanisms of action.

References

  1. Baselga, J. et al. Phase II study of weekly intravenous recombinant humanized anti-p185 (HER2) monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J. Clin. Oncol. 14, 737–744 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Haseltine, W. A. Not quite pharmacogenomics. Nature Biotechnol. 16, 1295 (1998).

  3. In, K. H. et al. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J. Clin. Invest. 99, 1130–1137 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. McGraw, D. W., Forbes, S. L., Kramer, L. A. & Liggett, S. B. Polymorphisms of the 5′ leader cistron of the human β2-adrenergic receptor regulate receptor expression. J. Clin. Invest. 102, 1927–1932 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Huang, Y. et al. The role of a mutant CCR5 allele in HIV-1 transmission and disease progression. Nature Med. 2, 1240–1243 (1996).

    Article  CAS  PubMed  Google Scholar 

  6. Dean, M. et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion of the CKR5 structural gene. Science 273, 1856–1862 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Samson, M. et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382, 722–725 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. O'Brien, T. R. et al. HIV-1 infection in a man homozygous for CCR5Δ32. Lancet 349, 1219 (1997).

    Article  CAS  PubMed  Google Scholar 

  9. Theodorou, I. et al. HIV-1 infection in an individual homozygous for CCR5Δ32. Lancet 349, 1219–1220 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Drazen, J. M. et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature Genet. 22, 168–170 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Martinez, F. D., Graves, P. E., Baldinim M., Solomon, S. & Erickson, R. Association between genetic polymorphisms of the β2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J. Clin. Invest. 100, 3184–3188 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tan, S., Hall, I. P., Dewar, J., Dow, E. & Lipworth, B. Association between β2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics. Lancet 350, 995–999 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. Green, S. A., Turki, J., Innis, M. & Liggett, S. B. Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33, 9414–9419 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Green, S. A., Turki, J., Bejarano, P., Hall, I. P. & Liggett, S. B. Influence of β2-adrenergic receptor genotypes on signal transduction in human airway smooth muscle cells. Am. J. Respir. Cell Mol. Biol. 13, 25–33 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. Reihsaus, E., Innis, M., MacIntyre, N. & Liggett, S. B. Mutations in the gene encoding for the β2-adrenergic receptor in normal and asthmatic subjects. Am. J. Respir. Cell Mol. Biol. 8, 334–349 (1993).

    Article  CAS  PubMed  Google Scholar 

  16. Dewar, J. C. et al. β2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population. Clin. Exp. Allergy 28, 442–448 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Fischel-Ghodsian, N. Genetic factors in aminoglycoside toxicity. Ann. NY Acad. Sci. 884, 99–109 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Hutchin, T. & Cortopassi, G. Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. Antimicrob. Agents Chemother. 38, 2517–2520 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Esteller, M. et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med. 343, 1350–1354 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Roses, A. Pharmacogenetics and future drug development and delivery. Lancet 355, 1358–1361 (2000).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Roche Genetics, F. Hoffmann-La Roche, Building 93/532, Basel, CH-4070, Switzerland

    Klaus Lindpaintner

Authors
  1. Klaus Lindpaintner
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

Cancer.gov

breast cancer

LocusLink

β2-adrenoceptor

CCR5

CXCR4

HER2

5-lipoxygenase

O6-methylguanine DNA methylase

12S ribosomal RNA

thiopurine methyltransferase

Medscape DrugInfo

trastuzamab

FURTHER INFORMATION

Encyclopedia of Life Sciences

pharmacogenetics

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lindpaintner, K. The impact of pharmacogenetics and pharmacogenomics on drug discovery. Nat Rev Drug Discov 1, 463–469 (2002). https://doi.org/10.1038/nrd823

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd823

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing