Genetic variation in P450c11AS in Chilean patients with low renin hypertension

The Journal of Clinical Endocrinology and Metabolism
C E FardellaW L Miller

Abstract

Low renin hypertension (LRH), which accounts for 10-20% of patients with idiopathic "essential" hypertension, bears hormonal similarities to mineralocorticoid-induced hypertension, but elevated mineralocorticoid concentrations have not been found. Some patients with LRH have normal, rather than suppressed, plasma aldosterone concentrations, so that the ratio of aldosterone concentration to PRA (Aldo/PRA) is high, suggesting inappropriately increased aldosterone biosynthesis. We characterized the CYP11B2 gene that encodes the aldosterone synthase, P450c11AS, in hypertensive and control populations in a single clinic in Santiago, Chile. We directly sequenced the entire CYP11B2 gene in 12 patients with LRH, 2 high renin hypertensive controls, and 2 normotensive controls. All sequences were identical, except that 8 of 24 LRH alleles encoded arginine rather than lysine at position 173. The Arg173 and Lys173 variants were expressed in transfected MA-10 cells, and their ability to convert deoxycorticosterone to aldosterone was measured; the apparent Michaelis constant (Km) for Lys173 was 2.73 mumol/L; the Km for Arg173 was 2.53 mumol/L. The apparent maximal velocity (Vmax) for Lys173 was 6.5 x 10(-3) micrograms/mL.24 h; the Vmax for A...Continue Reading

Citations

Nov 1, 2001·Proceedings of the National Academy of Sciences of the United States of America·K RanadeD Botstein
Nov 6, 2010·Endocrine Reviews·Walter L Miller, Richard J Auchus
Jul 17, 2010·Journal of Endocrinological Investigation·C A CarvajalC E Fardella
May 1, 2008·Journal of Neurology·David BrennerUNKNOWN GENIC Investigators
Oct 14, 2008·Molecular and Cellular Endocrinology·Eleanor DaviesJohn M C Connell
Jul 27, 2001·Best Practice & Research. Clinical Endocrinology & Metabolism·J M ConnellE Davies
Dec 1, 2004·Kidney International·Kushiar ShojaatiMarkus G Mohaupt
Mar 17, 2000·The Journal of Clinical Endocrinology and Metabolism·A FisherE Davies
Jul 18, 2019·Frontiers in Pediatrics·Rupesh RainaKirsten Kusumi
May 24, 2020·Journal of Clinical Medicine·Łukasz ŻukowskiJanusz Myśliwiec

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