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Spyroglou, A.* ; Bozoglu, T.* ; Rawal, R. ; de Leonardis, F.* ; Sterner, C.* ; Boulkroun, S.* ; Benecke, A.G.* ; Monti, L.* ; Zennaro, M.C.* ; Petersen, A.-K. ; Döring, A. ; Rossi, A.* ; Bidlingmaier, M.* ; Warth, R.* ; Gieger, C. ; Reincke, M.* ; Beuschlein, F.*

Diastrophic dysplasia sulfate transporter (SLC26A2) is expressed in the adrenal cortex and regulates aldosterone secretion.

Hypertension 63, 1102-1109 (2014)
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Elucidation of the molecular mechanisms leading to autonomous aldosterone secretion is a prerequisite to define potential targets and biomarkers in the context of primary aldosteronism. After a genome-wide association study with subjects from the population-based Cooperative Health Research in the Region of Augsburg F4 survey, we observed a highly significant association (P=6.78×10(-11)) between the aldosterone to renin ratio and a locus at 5q32. Hypothesizing that this locus may contain genes of relevance for the pathogenesis of primary aldosteronism, we investigated solute carrier family 26 member 2 (SLC26A2), a protein with known transport activity for sulfate and other cations. Within murine tissues, adrenal glands showed the highest expression levels for SLC26A2, which was significantly downregulated on in vivo stimulation with angiotensin II and potassium. SLC26A2 expression was found to be significantly lower in aldosterone-producing adenomas in comparison with normal adrenal glands. In adrenocortical NCI-H295R cells, specific knockdown of SLC26A2 resulted in a highly significant increase in aldosterone secretion. Concomitantly, expression of steroidogenic enzymes, as well as upstream effectors including transcription factors such as NR4A1, CAMK1, and intracellular Ca(2+) content, was upregulated in knockdown cells. To substantiate further these findings in an SLC26A2 mutant mouse model, aldosterone output proved to be increased in a sex-specific manner. In summary, these findings point toward a possible effect of SLC26A2 in the regulation of aldosterone secretion potentially involved in the pathogenesis of primary aldosteronism.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Aldosterone To Renin Ratio ; Calcium Signaling ; Genome-wide Association Study ; Knockout Mice ; Primary Hyperaldosteronism ; Solute Carrier Family 26 (sulfate Transporter), Member 2 Protein, Human; Association Analyses Identify; Genome-wide Association; Blood-pressure; Somatic Mutations; Channel Mutations; Kcnj5 Mutations; Ca2+ Channels; Renin Ratio; Hypertension; Adenomas
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 0194-911x
e-ISSN 1524-4563
Zeitschrift Hypertension
Quellenangaben Band: 63, Heft: 5, Seiten: 1102-1109 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Philadelphia
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504100-001
G-504000-002
PubMed ID 24591336
DOI 10.1161/HYPERTENSIONAHA.113.02504
WOS ID WOS:000334320900042
Scopus ID 84902273027
Erfassungsdatum 2014-03-13
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