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

• Published in: The pharmacogenomics journal Vol. 16; no. 1; pp. 3 - 9
• Main Authors: Sanada, H, Yoneda, M, Yatabe, J, Williams, S M, Bartlett, J, White, M J, Gordon, L N, Felder, R A, Eisner, G M, Armando, I, Jose, P A
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.02.2016
• Subjects: Aged; Aged, 80 and over; Angiotensin; Angiotensin II receptor blockers; Angiotensin Receptor Antagonists - therapeutic use; Asian Continental Ancestry Group; Blood pressure; Blood Pressure - drug effects; Case-Control Studies; Development and progression; Dosage and administration; Drug metabolism; Female; Genetic aspects; Genetic Association Studies; Genetic Loci; Genetic Markers; Haplotypes; Humans; Hypertension; Hypertension - drug therapy; Hypertension - genetics; Hypertension - physiopathology; Male; Middle Aged; Polymorphism, Single Nucleotide; Population studies; Receptors, G-Protein-Coupled - genetics
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2015.6

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.