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Gene mutations that promote adrenal aldosterone production, sodium retention, and hypertension

Authors Moraitis A, Rainey W, Auchus R

Received 15 August 2013

Accepted for publication 16 October 2013

Published 24 December 2013 Volume 2014:7 Pages 1—13

DOI https://doi.org/10.2147/TACG.S35571

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5


Andreas G Moraitis,1 William E Rainey,1,2 Richard J Auchus1

1Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, 2Department of Physiology, University of Michigan, Ann Arbor, MI, USA

Abstract: Primary aldosteronism (PA) is the most common form of secondary hypertension, found in about 5% of all hypertension cases, and up to 20% of resistant hypertension cases. The most common forms of PA are an aldosterone-producing adenoma and idiopathic (bilateral) hyperaldosteronism. Rare genetic forms of PA exist and, until recently, the only condition with a known genetic mechanism was familial hyperaldosteronism type 1, also known as glucocorticoid-remediable aldosteronism (FHA1/GRA). FHA type 3 has now been shown to derive from germline mutations in the KCNJ5 gene, which encodes a potassium channel found on the adrenal cells. Remarkably, somatic mutations in KCNJ5 are found in about one-third of aldosterone-producing adenomas, and these mutations are likely to be involved in their pathogenesis. Finally, mutations in the genes encoding an L-type calcium channel (CACNA1D) and in genes encoding a sodium–potassium adenosine triphosphatase (ATP1A1) or a calcium adenosine triphosphatase (ATP2B3) are found in other aldosterone-producing adenomas. These findings provide a working model, in which adenoma formation and/or aldosterone production in many cases derives from increased calcium entry, which drives the pathogenesis of primary aldosteronism.

Keywords: hyperaldosteronism, hereditary, potassium channel, calcium channel

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