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  • Review Article
  • Published:

Hypertension pharmacogenomics: in search of personalized treatment approaches

Nature Reviews Nephrology volume 12, pages 110–122 (2016)Cite this article

Subjects

Key Points

  • Hypertension is an important, modifiable risk factor for cardiovascular and kidney disease

  • Rates of blood pressure control are substantially below the desired levels globally, with many factors contributing to poor blood pressure control

  • Pharmacogenomics and other 'omics' approaches could help to identify useful biomarkers for a more personalized or precision approach to antihypertensive treatment strategies

  • Validating and replicating antihypertensive pharmacogenomics signals will require large sample sizes and will probably not yield a single signal with a large effect size, but rather multiple signals with small effect sizes

  • As technology continues to evolve and genetic and other 'omics' data become available from collaborative studies, identification of biomarkers of blood pressure response might be possible

Abstract

Cardiovascular and renal diseases are associated with many risk factors, of which hypertension is one of the most prevalent. Worldwide, blood pressure control is only achieved in ∼50% of those treated for hypertension, despite the availability of a considerable number of antihypertensive drugs from different pharmacological classes. Although many reasons exist for poor blood pressure control, a likely contributor is the inability to predict to which antihypertensive drug an individual is most likely to respond. Hypertension pharmacogenomics and other 'omics' technologies have the potential to identify genetic signals that are predictive of response or adverse outcome to particular drugs, and guide selection of hypertension treatment for a given individual. Continued research in this field will enhance our understanding of how to maximally deploy the various antihypertensive drug classes to optimize blood pressure response at the individual level. This Review summarizes the available literature on the most convincing genetic signals associated with antihypertensive drug responses and adverse cardiovascular outcomes. Future research in this area will be facilitated by enhancing collaboration between research groups through consortia such as the International Consortium for Antihypertensives Pharmacogenomics Studies, with the goal of translating replicated findings into clinical implementation.

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Figure 1: The effect of ADRB1 haplotype on treatment response in patients with hypertension.
Figure 2: The effect of PRKCA genotype on blood pressure response to hydrochlorothiazide in participants from five independent studies (PEAR, GERA, NORDIL, GENRES and MILAN).
Figure 3: Development of a genetic risk-score associated with treatment-related adverse cardiovascular outcomes on the basis of data from the INVEST and NORDIL trials.

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Acknowledgements

R.M.C.-D. has received grant funding from NIH, NIGMS U01 GM074492 and U01 GM092586; and NIH, NHGRI U01 HG007269. J.A.J. has received grant funding from NIH, NIGMS U01 GM074492; NIH, NHGRI U01 HG007269, and NIH, NINDS R01 NS073346 and FDA U01 FD005235.

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  1. Department of Pharmacotherapy and Translational Research and Division of Cardiovascular Medicine, Colleges of Pharmacy and Medicine, University of Florida, PO Box 100484, 1600 SW Archer Road, Gainesville, 32610–0484, Florida, USA

    Rhonda M. Cooper-DeHoff & Julie A. Johnson

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  1. Rhonda M. Cooper-DeHoff
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  2. Julie A. Johnson
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Both authors researched data for the article, made substantial contributions to planning the review, shared in the writing of the article and reviewed or edited the manuscript before and after submission.

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Correspondence to Julie A. Johnson.

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The authors declare no competing financial interests.

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Cooper-DeHoff, R., Johnson, J. Hypertension pharmacogenomics: in search of personalized treatment approaches. Nat Rev Nephrol 12, 110–122 (2016). https://doi.org/10.1038/nrneph.2015.176

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