X-chromosome variants are associated with aldosterone producing adenomas

Abstract Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To da...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ravi Kumar Dutta, Malin Larsson, Thomas Arnesen, Anette Heie, Martin Walz, Piero Alesina, Oliver Gimm, Peter Söderkvist
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4f78aad9b98748638c71ffa0c7923501
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4f78aad9b98748638c71ffa0c7923501
record_format	dspace
spelling	oai:doaj.org-article:4f78aad9b98748638c71ffa0c79235012021-12-02T15:45:27ZX-chromosome variants are associated with aldosterone producing adenomas10.1038/s41598-021-89986-82045-2322https://doaj.org/article/4f78aad9b98748638c71ffa0c79235012021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89986-8https://doaj.org/toc/2045-2322Abstract Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To date, no studies have used a genome-wide association study (GWAS) approach to search for predisposing loci for APAs. Thus, we investigated Scandinavian APA cases (n = 35) and Swedish controls (n = 60) in a GWAS and discovered a susceptibility locus on chromosome Xq13.3 (rs2224095, OR = 7.9, 95% CI = 2.8–22.4, P = 1 × 10–7) in a 4-Mb region that was significantly associated with APA. Direct genotyping of sentinel SNP rs2224095 in a replication cohort of APAs (n = 83) and a control group (n = 740) revealed persistently strong significance (OR = 6.1, 95% CI = 3.5–10.6, p < 0.0005). We sequenced an adjacent gene, MAGEE1, of the sentinel SNP and identified a rare variant in one APA, p.Gly327Glu, which is complementary to other mutations in our primary cohort. Expression quantitative trait loci (eQTL) were investigated on the X-chromosome, and 24 trans-eQTL were identified. Some of the genes identified by trans-eQTL point towards a novel mechanistic explanation for the association of the SNPs with APAs. In conclusion, our study provides further insights into the genetic basis of APAs.Ravi Kumar DuttaMalin LarssonThomas ArnesenAnette HeieMartin WalzPiero AlesinaOliver GimmPeter SöderkvistNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ravi Kumar Dutta Malin Larsson Thomas Arnesen Anette Heie Martin Walz Piero Alesina Oliver Gimm Peter Söderkvist X-chromosome variants are associated with aldosterone producing adenomas
description	Abstract Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To date, no studies have used a genome-wide association study (GWAS) approach to search for predisposing loci for APAs. Thus, we investigated Scandinavian APA cases (n = 35) and Swedish controls (n = 60) in a GWAS and discovered a susceptibility locus on chromosome Xq13.3 (rs2224095, OR = 7.9, 95% CI = 2.8–22.4, P = 1 × 10–7) in a 4-Mb region that was significantly associated with APA. Direct genotyping of sentinel SNP rs2224095 in a replication cohort of APAs (n = 83) and a control group (n = 740) revealed persistently strong significance (OR = 6.1, 95% CI = 3.5–10.6, p < 0.0005). We sequenced an adjacent gene, MAGEE1, of the sentinel SNP and identified a rare variant in one APA, p.Gly327Glu, which is complementary to other mutations in our primary cohort. Expression quantitative trait loci (eQTL) were investigated on the X-chromosome, and 24 trans-eQTL were identified. Some of the genes identified by trans-eQTL point towards a novel mechanistic explanation for the association of the SNPs with APAs. In conclusion, our study provides further insights into the genetic basis of APAs.
format	article
author	Ravi Kumar Dutta Malin Larsson Thomas Arnesen Anette Heie Martin Walz Piero Alesina Oliver Gimm Peter Söderkvist
author_facet	Ravi Kumar Dutta Malin Larsson Thomas Arnesen Anette Heie Martin Walz Piero Alesina Oliver Gimm Peter Söderkvist
author_sort	Ravi Kumar Dutta
title	X-chromosome variants are associated with aldosterone producing adenomas
title_short	X-chromosome variants are associated with aldosterone producing adenomas
title_full	X-chromosome variants are associated with aldosterone producing adenomas
title_fullStr	X-chromosome variants are associated with aldosterone producing adenomas
title_full_unstemmed	X-chromosome variants are associated with aldosterone producing adenomas
title_sort	x-chromosome variants are associated with aldosterone producing adenomas
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4f78aad9b98748638c71ffa0c7923501
work_keys_str_mv	AT ravikumardutta xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT malinlarsson xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT thomasarnesen xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT anetteheie xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT martinwalz xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT pieroalesina xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT olivergimm xchromosomevariantsareassociatedwithaldosteroneproducingadenomas AT petersoderkvist xchromosomevariantsareassociatedwithaldosteroneproducingadenomas
_version_	1718385747843612672

X-chromosome variants are associated with aldosterone producing adenomas

Ejemplares similares