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.
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 GRK4(142V), 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 hGRK4(142V) had a greater decrease in systolic BP in response to ARBs than non-carrier hypertensive patients. By contrast, those with variants only at GRK4(486V) 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 GRK4(142V) and a larger decrease in BP with ARBs in hypertensive patients.
Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan.|Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan.
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Sanada
Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan.|Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan.
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Yoneda
Division of Health Science Research, Fukushima Welfare Federation of Agricultural Cooperatives, Fukushima, Japan.|Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, Fukushima, Japan.
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Yatabe
Department of Molecular Physiology and Biophysics and Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
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Williams
Department of Molecular Physiology and Biophysics and Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
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Bartlett
Department of Molecular Physiology and Biophysics and Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
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MJ
White
Department of Molecular Physiology and Biophysics and Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN, USA.|Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
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Gordon
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, USA.
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Felder
Department of Medicine, Georgetown University Medical Center, Washington, DC, USA.
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Eisner
Division of Nephrology, Department of Medicine, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
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Armando
Division of Nephrology, Department of Medicine, and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
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Jose
D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
D057911:Angiotensin Receptor Antagonists; C091670:GPR4 protein, human; D005819:Genetic Markers; D043562:Receptors, G-Protein-Coupled