Beuschlein, Felix and Boulkroun, Sheerazed and Osswald, Andrea and Wieland, Thomas and Nielsen, Hang N. and Lichtenauer, Urs D. and Penton, David and Schack, Vivien R. and Amar, Laurence and Fischer, Evelyn and Walther, Anett and Tauber, Philipp and Schwarzmayr, Thomas and Diener, Susanne and Graf, Elisabeth and Allolio, Bruno and Samson-Couterie, Benoit and Benecke, Arndt and Quinkler, Marcus and Fallo, Francesco and Plouin, Pierre-Francois and Mantero, Franco and Meitinger, Thomas and Mulatero, Paolo and Jeunemaitre, Xavier and Warth, Richard and Vilsen, Bente and Zennaro, Maria-Christina and Strom, Tim M. and Reincke, Martin (2013) Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone-producing adenomas and secondary hypertension. NATURE GENETICS, 45 (4). pp. 440-444. ISSN 1061-4036,
Full text not available from this repository. (Request a copy)Abstract
Primary aldosteronism is the most prevalent form of secondary hypertension. To explore molecular mechanisms of autonomous aldosterone secretion, we performed exome sequencing of aldosterone-producing adenomas (APAs). We identified somatic hotspot mutations in the ATP1A1 (encoding an Na+/K+ ATPase (1 subunit) and ATP2B3 (encoding a Ca2+ ATPase) genes in three and two of the nine APAs, respectively. These ATPases are expressed in adrenal cells and control sodium, potassium and calcium ion homeostasis. Functional in vitro studies of ATP1A1 mutants showed loss of pump activity and strongly reduced affinity for potassium. Electrophysiological ex vivo studies on primary adrenal adenoma cells provided further evidence for inappropriate depolarization of cells with ATPase alterations. In a collection of 308 APAs, we found 16(5.2%) somatic mutations in ATP1A1 and 5 (1.6%) in ATP2B3. Mutation-positive cases showed male dominance, increased plasma aldosterone concentrations and lower potassium concentrations compared with mutationnegative cases. In summary, dominant somatic alterations in two members of the ATPase gene family result in autonomous aldosterone secretion.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ZONA GLOMERULOSA; KCNJ5 MUTATIONS; PATHWAYS; ATPASE; PUMP; NA,K-ATPASE; PREVALENCE; CELLS; MICE; K+; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Richard Warth |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2020 08:25 |
| Last Modified: | 20 Apr 2020 08:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16939 |
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