Novel genetic determinants of adrenal aldosterone regulation

Azizan Elena Aisha, Morris J. Brown

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Purpose of review Aldosterone regulation in the adrenal plays an important role in blood pressure. The commonest curable cause of hypertension is primary aldosteronism. Recently, mutations in novel genes have been identified to cause primary aldosteronism. Elucidating the mechanism of action of these genetic abnormalities may help understand the cause of primary aldosteronism and the physiological regulation of aldosterone in the zona glomerulosa. Recent findings KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1, and CACNA1H mutations are causal of primary aldosteronism. ARMC5 may cause bilateral lesions resulting in primary aldosteronism. LGR5, DACH1, and neuron-specific proteins are highly expressed in the zona glomerulosa and regulate aldosterone production. Summary Most mutations causing primary aldosteronism are in genes encoding cation channels or pumps, leading to increased calcium influx. Genotype-phenotype analyses identified two broad subtypes of aldosterone-producing adenomas (APAs), zona fasciculata-like and zona glomerulosa-like, and the likelihood of under-diagnosed zona glomerulosa-like APAs because of small size. Zona fasciculata-like APAs are only associated with KCNJ5 mutations, whereas zona glomerulosa-like APAs are associated with mutations in ATPase pumps, CACNA1D, and CTNNB1. The frequency of APAs, and the multiplicity of causal mutations, suggests a pre-existing drive for these mutations. We speculate that these mutations are selected for protecting against tonic inhibition of aldosterone in human zona glomerulosa, which express genes inhibiting aldosterone production.

Original languageEnglish
Pages (from-to)209-217
Number of pages9
JournalCurrent Opinion in Endocrinology, Diabetes and Obesity
Volume23
Issue number3
DOIs
Publication statusPublished - 1 Jun 2016

Fingerprint

Aldosterone
Zona Glomerulosa
Hyperaldosteronism
Mutation
Adenoma
Zona Fasciculata
Genes
Adenosine Triphosphatases
Cations
Genotype
Blood Pressure
Hypertension
Calcium
Phenotype
Neurons

Keywords

  • adrenal
  • aldosterone
  • aldosterone-producing adenoma
  • primary aldosteronism
  • zona glomerulosa

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine
  • Nutrition and Dietetics

Cite this

Novel genetic determinants of adrenal aldosterone regulation. / Elena Aisha, Azizan; Brown, Morris J.

In: Current Opinion in Endocrinology, Diabetes and Obesity, Vol. 23, No. 3, 01.06.2016, p. 209-217.

Research output: Contribution to journalReview article

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