Identification of risk loci for primary aldosteronism in genome-wide association studies
Edith Le Floch
(1, 2)
,
Teresa Cosentino
(3)
,
Casper K Larsen
(3)
,
Felix Beuschlein
(4, 5)
,
Martin Reincke
(4)
,
Laurence Amar
(3, 6)
,
Gian-Paolo Rossi
(7)
,
Kelly de Sousa
(3)
,
Stéphanie Baron
(6, 8)
,
Sophie Chantalat
(1, 2)
,
Benjamin Saintpierre
(9)
,
Livia Lenzini
(7)
,
Arthur Frouin
(1, 2)
,
Isabelle Giscos-Douriez
(3)
,
Matthis Ferey
(3)
,
Alaa B Abdellatif
(3)
,
Tchao Meatchi
(3, 6)
,
Jean-Philippe Empana
(3)
,
Xavier Jouven
(3, 6)
,
Christian Gieger
(10, 11)
,
Melanie Waldenberger
(10, 12)
,
Annette Peters
(10, 11, 12)
,
Daniele Cusi
(13)
,
Erika Salvi
(14)
,
Pierre Meneton
(15)
,
Mathilde Touvier
(16)
,
Mélanie Deschasaux
(16)
,
Nathalie Druesne-Pecollo
(16)
,
Sheerazed Boulkroun
(3)
,
Fabio L Fernandes-Rosa
(3)
,
Jean-François Deleuze
(1, 2)
,
Xavier Jeunemaitre
(3, 6)
,
Maria-Christina Zennaro
(3, 6)
1
CNRGH -
Centre National de Recherche en Génomique Humaine
2 JACOB - Institut de Biologie François JACOB
3 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
4 LMU - Ludwig-Maximilians University [Munich]
5 UZH - Universität Zürich [Zürich] = University of Zurich
6 HEGP - Hôpital Européen Georges Pompidou [APHP]
7 Unipd - Università degli Studi di Padova = University of Padua
8 UPCité - Université Paris Cité
9 IC UM3 (UMR 8104 / U1016) - Institut Cochin
10 Helmholtz Zentrum München = German Research Center for Environmental Health
11 DZD - German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg]
12 DZHK - German Center for Cardiovascular Research
13 CNR - Consiglio Nazionale delle Ricerche [Milano]
14 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
15 LIMICS - Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé
16 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
2 JACOB - Institut de Biologie François JACOB
3 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
4 LMU - Ludwig-Maximilians University [Munich]
5 UZH - Universität Zürich [Zürich] = University of Zurich
6 HEGP - Hôpital Européen Georges Pompidou [APHP]
7 Unipd - Università degli Studi di Padova = University of Padua
8 UPCité - Université Paris Cité
9 IC UM3 (UMR 8104 / U1016) - Institut Cochin
10 Helmholtz Zentrum München = German Research Center for Environmental Health
11 DZD - German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg]
12 DZHK - German Center for Cardiovascular Research
13 CNR - Consiglio Nazionale delle Ricerche [Milano]
14 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
15 LIMICS - Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé
16 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
Felix Beuschlein
- Function : Author
- PersonId : 758956
- ORCID : 0000-0001-7826-3984
Martin Reincke
- Function : Author
- PersonId : 758957
- ORCID : 0000-0002-9817-9875
Melanie Waldenberger
- Function : Author
- PersonId : 1183980
- ORCID : 0000-0003-0583-5093
Erika Salvi
- Function : Author
- PersonId : 1183981
- ORCID : 0000-0002-2724-2291
Pierre Meneton
- Function : Author
- PersonId : 849663
- IdHAL : pierre-meneton
- ORCID : 0000-0003-4611-1892
Mathilde Touvier
- Function : Author
- PersonId : 1136541
Sheerazed Boulkroun
- Function : Author
- PersonId : 1183982
- ORCID : 0000-0002-8796-7534
Fabio L Fernandes-Rosa
- Function : Author
- PersonId : 794608
- ORCID : 0000-0002-0162-0792
Jean-François Deleuze
- Function : Author
- PersonId : 798476
- ORCID : 0000-0002-5358-4463
Xavier Jeunemaitre
- Function : Author
- PersonId : 756353
- ORCID : 0000-0001-5925-381X
Maria-Christina Zennaro
- Function : Author
- PersonId : 764446
- ORCID : 0000-0001-5449-9191
- IdRef : 105967475
Abstract
Abstract 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.
Origin : Publication funded by an institution