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Update on the Genetics of Primary Aldosteronism and Aldosterone-Producing Adenomas

  • Hypertension (DS Geller and DL Cohen, Section Editors)
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Abstract

Purpose of the Review

Primary aldosteronism (PA) is the leading cause of secondary hypertension, accounting for over 10% of patients with high blood pressure. It is characterized by autonomous production of aldosterone from the adrenal glands leading to low-renin levels. The two most common forms arise from bilateral adrenocortical hyperplasia (BAH) and aldosterone-producing adenoma (APA). We discuss recent discoveries in the genetics of PA.

Recent Findings

Most APAs harbor variants in the KCNJ5, CACNA1D, ATP1A1, ATP2B3, and CTNNB1 genes. With the exception of β-catenin (CTNNB1), all other causative genes encode ion channels; pathogenic variants found in PA lead to altered ion transportation, cell membrane depolarization, and consequently aldosterone overproduction. Some of these genes are found mutated in the germline state (CYP11B2, CLCN2, KCNJ5, CACNA1H, and CACNA1D), leading then to familial hyperaldosteronism, and often BAH rather than single APAs.

Summary

Several genetic defects in the germline or somatic state have been identified in PA. Understanding how these molecular abnormalities lead to excess aldosterone contributes significantly to the elucidation of the pathophysiology of low-renin hypertension. It may also lead to new and more effective therapies for this disease acting at the molecular level.

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Acknowledgements

The authors would like to thank Yolanda L. Jones, National Institutes of Health Library, for editing assistance.

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Authors and Affiliations

  1. Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Georgia Pitsava

  2. Section On Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Georgia Pitsava, Fabio R. Faucz, Constantine A. Stratakis & Fady Hannah-Shmouni

  3. ELPEN Pharmaceuticals, Pikermi, Athens, Greece

    Constantine A. Stratakis

  4. Human Genetics & Precision Medicine, IMBB, FORTH, Heraklion, Greece

    Constantine A. Stratakis

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  1. Georgia Pitsava
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Correspondence to Fady Hannah-Shmouni.

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Conflicts of Interest

Dr. Hannah-Shmouni is a member of the Endocrine Hypertension Subcommittee of the Canadian Hypertension Guidelines (Hypertension Canada) and has no relevant disclosures to report. Dr. Stratakis holds patents on the PRKAR1A, PDE11A, and GPR101 genes and/or their function and has received research funding from Pfizer Inc. on the genetics and treatment of abnormalities of growth hormone secretion. Dr. Stratakis is currently employed by ELPEN Pharmaceuticals and has received consulting fees from Sync, Lundbeck, and Sandoz. Dr. Stratakis also reports grant support from the NIH. Dr. Faucz holds a patent on the GPR101 gene and its function. Dr. Pitsava has no conflicts of interest.

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Pitsava, G., Faucz, F.R., Stratakis, C.A. et al. Update on the Genetics of Primary Aldosteronism and Aldosterone-Producing Adenomas. Curr Cardiol Rep 24, 1189–1195 (2022). https://doi.org/10.1007/s11886-022-01735-z

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