The molecular basis of primary aldosteronism: from chimeric gene to channelopathy

Curr Opin Pharmacol. 2015 Apr:21:35-42. doi: 10.1016/j.coph.2014.12.005. Epub 2014 Dec 30.

Abstract

Primary aldosteronism (PA) is the most common endocrine cause of high blood pressure. Only a minority of the PA cases are familial and due to known (CYP11B2/CYP11B1 chimeric gene or mutations in the KCNJ5 gene) or unknown causes. In the most common sporadic cases the mechanisms by which the excess aldosterone production persists in spite of high blood pressure, sodium retention, suppression of the renin angiotensin system and low potassium levels, all factors that by themselves would be expected to shut off aldosterone production, were a puzzle for decades. Only recently the discovery of functional mutations and down-regulation of potassium channels provided some explanations. We herein reviewed these recent findings and their mechanistic implications. We also propose a clinical molecular classification of familial hyperaldosteronism, which can be important from the practical standpoint as it considers besides the molecular features also the responsiveness to treatment and the imaging features.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Channelopathies
  • Cytochrome P-450 CYP11B2 / genetics
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics
  • Humans
  • Hyperaldosteronism* / genetics
  • Hyperaldosteronism* / immunology
  • Hyperaldosteronism* / metabolism
  • Mutant Chimeric Proteins / genetics
  • Potassium Channels, Tandem Pore Domain / physiology
  • Steroid 11-beta-Hydroxylase / genetics

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • KCNJ5 protein, human
  • Mutant Chimeric Proteins
  • Potassium Channels, Tandem Pore Domain
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase