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Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade

The Pharmacogenomics Journal volume 16, pages 3–9 (2016)Cite this article

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Abstract

Non-synonymous GRK4 variants, R65L, A142V and A486V, are associated with essential hypertension in diverse populations. This study replicated the association of GRK4 variants, including GRK4142V, with human essential hypertension in a Japanese population (n=588; hypertensive, n=486 normotensive controls) and determined whether the presence of GRK4 variants predicted the blood pressure (BP) response to angiotensin receptor blockers (ARBs) in patients with essential hypertension. We analyzed 829 patients and compared the response to ARBs between individuals with no GRK4 variants (n=136) and those with variants at one or any of the three loci (n=693). Carriers of hGRK4142V had a greater decrease in systolic BP in response to ARBs than non-carrier hypertensive patients. By contrast, those with variants only at GRK4486V were less likely to achieve the BP goal in response to an ARB than those with no variants. These studies showed for the first time the association between GRK4142V and a larger decrease in BP with ARBs in hypertensive patients.

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Acknowledgements

The work was funded by grants from the US National Institutes of Health, P01HL074940, P01HL068686, R01HL092196, R37HL023081, R01DK039308, and DK090918. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ethics Statement: The Institutional Review Board at the Fukushima Medical University approved all protocols.

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Authors and Affiliations

  1. Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan

    H Sanada, M Yoneda & J Yatabe

  2. Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan

    H Sanada, M Yoneda & J Yatabe

  3. Department of Molecular Physiology and Biophysics and Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA

    S M Williams, J Bartlett, M J White & L N Gordon

  4. Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA

    S M Williams, J Bartlett, M J White & L N Gordon

  5. Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, USA

    R A Felder

  6. Department of Medicine, Georgetown University Medical Center, Washington, DC, USA

    G M Eisner

  7. Division of Nephrology, Department of Medicine, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA

    I Armando & P A Jose

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  1. H Sanada
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Correspondence to P A Jose.

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Competing interests

Drs Jose and Felder own Hypogen, Inc., which owns the US Patent (6,660,474B1) for GRK4. Drs. Eisner and Williams are members of the Board of Hypogen, Inc.

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Sanada, H., Yoneda, M., Yatabe, J. et al. Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade. Pharmacogenomics J 16, 3–9 (2016). https://doi.org/10.1038/tpj.2015.6

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