Identification of risk loci for primary aldosteronism in genome-wide association studies

被引：26

作者：

Le Floch, Edith ^{[1
]}

Cosentino, Teresa ^{[2
]}

Larsen, Casper K. ^{[2
]}

Beuschlein, Felix ^{[3
,4
,5
]}

Reincke, Martin ^{[3
]}

Amar, Laurence ^{[2
,6
]}

Rossi, Gian-Paolo ^{[7
]}

De Sousa, Kelly ^{[2
]}

Baron, Stephanie ^{[8
,9
]}

Chantalat, Sophie ^{[1
]}

Saintpierre, Benjamin ^{[10
]}

Lenzini, Livia ^{[7
]}

Frouin, Arthur ^{[1
]}

Giscos-Douriez, Isabelle ^{[2
]}

Ferey, Matthis ^{[2
]}

Abdellatif, Alaa B. ^{[2
]}

Meatchi, Tchao ^{[2
,11
]}

Empana, Jean-Philippe ^{[2
]}

Jouven, Xavier ^{[2
,12
]}

Gieger, Christian ^{[13
,14
,15
]}

Waldenberger, Melanie ^{[13
,14
,16
]}

Peters, Annette ^{[14
,15
,16
]}

Cusi, Daniele ^{[17
,18
]}

Salvi, Erika ^{[19
]}

Meneton, Pierre ^{[20
]}

Touvier, Mathilde ^{[21
]}

Deschasaux, Melanie ^{[21
]}

Druesne-Pecollo, Nathalie ^{[21
]}

Boulkroun, Sheerazed ^{[2
]}

Fernandes-Rosa, Fabio L. ^{[2
]}

Deleuze, Jean-Francois ^{[1
]}

Jeunemaitre, Xavier ^{[2
,22
]}

Zennaro, Maria-Christina ^{[2
,22
]}

机构：

[1] Univ Paris Saclay, Ctr Natl Rech Genom Humaine, Inst Biol Francois Jacob, CEA, Evry, France

[2] Univ Paris Cite, PARCC, Inserm, F-75015 Paris, France

[3] Ludwig Maximilians Univ Munchen, Med Klin & Poliklin 4, D-80336 Munich, Germany

[4] Univ Spital Zurich USZ, Klin Endokrinol Diabetol & Klin Ernahrung, Zurich, Switzerland

[5] Univ Zurich UZH, Zurich, Switzerland

[6] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Unite Hypertens Arterielle, Paris, France

[7] DMCSG G Patrassi Univ Padova, Univ Hosp, Med Sch, I-35126 Padua, Italy

[8] Univ Paris Cite, F-75006 Paris, France

[9] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv Physiol, Paris, France

[10] Univ Paris Cite, Inst Cochin, CNRS, INSERM,Genom IC Platform, F-75014 Paris, France

[11] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv Anat Pathol, Paris, France

[12] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv Cardiol, Paris, France

[13] German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany

[14] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany

[15] German Ctr Diabet Res DZD, Neuherberg, Germany

[16] German Res Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany

[17] Natl Res Council Italy, Inst Biomed Technol, Milan, Italy

[18] Bio4Dreams Business Nursery Life Sci, Milan, Italy

[19] Fdn IRCCS Ist Neurol Carlo Besta, Neuroalgol Unit, Milan, Italy

[20] Univ Paris 13, Sorbonne Univ, INSERM, UMR 1142, Paris, France

[21] Univ Paris Cite CRESS, Epidemiol & Stat Res Ctr, Nutr Epidemiol Res Team EREN, CNAM,INSERM U1153,INRAe U1125,Sorbonne Paris Nord, F-93017 Bobigny, France

[22] Hop Europeen Georges Pompidou, Assistance Publ Hop Paris, Serv Genet, Paris, France

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

欧盟地平线“2020”; 欧洲研究理事会;

关键词：

BLOOD-PRESSURE REGULATION; K+ CHANNEL MUTATIONS; SOMATIC MUTATIONS; PRIMARY HYPERALDOSTERONISM; RESISTANT HYPERTENSION; GLOBAL BURDEN; PREVALENCE; COMMON; METAANALYSIS; VARIANTS;

D O I：

10.1038/s41467-022-32896-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Detection of primary aldosteronism, the most common form of secondary arterial hypertension, is essential for targeted management and prevention of cardiovascular complications. Here, the authors identify genetic loci associated with primary aldosteronism, suggesting new mechanisms of disease.

引用

页数：17

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