Identification of risk loci for primary aldosteronism in genome-wide association studies.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 09 2022
03 09 2022
Historique:
received:
27
05
2021
accepted:
23
08
2022
entrez:
3
9
2022
pubmed:
4
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma. Candidate genes located within the two loci, CASZ1 and RXFP2, are expressed in human and mouse adrenals in different cell clusters. Their overexpression in adrenocortical cells suppresses mineralocorticoid output under basal and stimulated conditions, without affecting cortisol biosynthesis. Our study identifies the first risk loci for primary aldosteronism and highlights new mechanisms for the development of aldosterone excess.
Identifiants
pubmed: 36057693
doi: 10.1038/s41467-022-32896-8
pii: 10.1038/s41467-022-32896-8
pmc: PMC9440917
doi:
Substances chimiques
CASZ1 protein, human
0
DNA-Binding Proteins
0
Transcription Factors
0
Aldosterone
4964P6T9RB
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5198Informations de copyright
© 2022. The Author(s).
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