Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker.

Hypertension
Stephen T TurnerEric Boerwinkle

Abstract

To identify genes influencing blood pressure response to an angiotensin II receptor blocker, single nucleotide polymorphisms identified by genome-wide association analysis of the response to candesartan were validated by opposite direction associations with the response to a thiazide diuretic, hydrochlorothiazide. We sampled 198 white and 193 blacks with primary hypertension from opposite tertiles of the race-sex-specific distributions of age-adjusted diastolic blood pressure response to candesartan. There were 285 polymorphisms associated with the response to candesartan at P<10(-4) in whites. A total of 273 of the 285 polymorphisms, which were available for analysis in a separate sample of 196 whites, validated for opposite direction associations with the response to hydrochlorothiazide (Fisher χ(2) 1-sided P=0.02). Among the 273 polymorphisms, those in the chromosome 11q21 region were the most significantly associated with response to candesartan in whites (eg, rs11020821 near FUT4, P=8.98 × 10(-7)), had the strongest opposite direction associations with response to hydrochlorothiazide (eg, rs3758785 in GPR83, P=7.10 × 10(-3)), and had the same direction associations with response to candesartan in the 193 blacks (eg, rs1692...Continue Reading

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Citations

Nov 10, 2012·Nature Biotechnology·Andrew R Harper, Eric J Topol
Jun 22, 2013·Pharmacogenetics and Genomics·Caroline F ThornTeri E Klein
Apr 4, 2015·International Journal of Cardiology·Payman Shahabi, Marie-Pierre Dubé
Nov 29, 2012·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Xiuqin NiR Stephanie Huang
Feb 7, 2015·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Claudia P CabreraMark J Caulfield
Aug 19, 2015·Clinical Physiology and Functional Imaging·Viktor Hamrefors
Nov 12, 2015·Pharmacogenomics·Sara LupoliCristina Barlassina
Jul 23, 2015·Current Hypertension Reports·Nihal El Rouby, Rhonda M Cooper-DeHoff
Apr 7, 2015·Seminars in Fetal & Neonatal Medicine·Timur AzhibekovIstvan Seri
Feb 20, 2015·Journal of Hypertension·Martina ChittaniCristina Barlassina
Apr 30, 2015·Journal of Hypertension·Cristina Menni
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Feb 19, 2017·Pharmacology & Therapeutics·Ge Zhang, Daniel W Nebert
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Sep 17, 2013·Journal of Cardiovascular Pharmacology and Therapeutics·Nicolás Roberto RoblesRoman Hernandez-Gallego
Jul 8, 2020·International Journal of Molecular Sciences·Jacek RyszAnna Gluba-Brzózka

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