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Cardiovascular pharmacogenomics and individualized drug therapy

Nature Reviews Cardiology volume 6, pages 632–638 (2009)Cite this article

Abstract

The goal of individualized drug therapy requires physicians to be able to accurately predict an individual's response to a drug. Both genetic and environmental factors are known to influence drug response. 'Pharmacogenetics' is the study of the role of inheritance in variation in drug response phenotypes. Pharmacogenetics is now moving genome-wide to become 'pharmacogenomics', resulting in the recognition of novel biomarkers for individual variation in drug response. This article reviews the development, promise and challenges facing pharmacogenomics, using examples of drugs used to treat or prevent cardiovascular disease.

Key Points

  • Genetic variation has an important role in explaining individual variation in drug response, and genetic analysis could help us provide appropriate care to individual patients

  • Historically, this type of study has been confined to candidate genes for proteins involved in known pharmacokinetic and pharmacodynamic pathways for the drug—that is, 'pharmacogenetics'

  • Pharmacokinetic pathways influence the concentration of a drug reaching its target

  • Pharmacodynamic pathways influence the drug target itself and signaling pathways downstream of the drug target

  • Our ability to perform genome-wide studies across the entire human genome has transformed 'pharmacogenetics' into 'pharmacogenomics'

  • Clinical trials are needed to assess the clinical utility of genotyping in drug therapy and to justify the cost of genetic testing in clinical practice

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Figure 1: Warfarin, which is metabolized by CYP2C9, inhibits the vitamin K cycle via actions on thiol-dependent enzymes, such as VKORC1, that are required for regeneration of active vitamin K.
Figure 2: Genome-wide association study data for statin-induced myopathy.
Figure 3: Diagrammatic representation of the use of a cell-line-based model system to identify and validate, both functionally and clinically, pharmacogenomic candidate genes.

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Acknowledgements

Supported in part by HL 84904 (Heart Failure Clinical Research Network), a Marie Ingalls Cardiovascular Career Development Award (N. L. Pereira), a PhRMA Foundation “Center of Excellence in Clinical Pharmacology” Award (R. M. Weinshilboum), and NIH grants UL1RR24150 (N. L. Pereira), R01 GM28157 (R. M. Weinshilboum), R01 CA132780 (R. M. Weinshilboum) and U01 GM61388 (The Pharmacogenetics Research Network). We thank L. Wussow for her assistance with the preparation of this manuscript.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Naveen L. Pereira

  2. Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA

    Richard M. Weinshilboum

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Correspondence to Naveen L. Pereira.

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Pereira, N., Weinshilboum, R. Cardiovascular pharmacogenomics and individualized drug therapy. Nat Rev Cardiol 6, 632–638 (2009). https://doi.org/10.1038/nrcardio.2009.154

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