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Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension

The importance of excess salt intake in the pathogenesis of hypertension is widely recognized. Blood pressure is controlled primarily by salt and water balance because of the infinite gain property of the kidney to rapidly eliminate excess fluid and salt. Up to fifty percent of patients with essenti...

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Autores principales: Citterio, Lorena, Simonini, Marco, Zagato, Laura, Salvi, Erika, Delli Carpini, Simona, Lanzani, Chiara, Messaggio, Elisabetta, Casamassima, Nunzia, Frau, Francesca, D'Avila, Francesca, Cusi, Daniele, Barlassina, Cristina, Manunta, Paolo
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090407/
https://www.ncbi.nlm.nih.gov/pubmed/21573014
http://dx.doi.org/10.1371/journal.pone.0019620
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author Citterio, Lorena
Simonini, Marco
Zagato, Laura
Salvi, Erika
Delli Carpini, Simona
Lanzani, Chiara
Messaggio, Elisabetta
Casamassima, Nunzia
Frau, Francesca
D'Avila, Francesca
Cusi, Daniele
Barlassina, Cristina
Manunta, Paolo
author_facet Citterio, Lorena
Simonini, Marco
Zagato, Laura
Salvi, Erika
Delli Carpini, Simona
Lanzani, Chiara
Messaggio, Elisabetta
Casamassima, Nunzia
Frau, Francesca
D'Avila, Francesca
Cusi, Daniele
Barlassina, Cristina
Manunta, Paolo
author_sort Citterio, Lorena
collection PubMed
description The importance of excess salt intake in the pathogenesis of hypertension is widely recognized. Blood pressure is controlled primarily by salt and water balance because of the infinite gain property of the kidney to rapidly eliminate excess fluid and salt. Up to fifty percent of patients with essential hypertension are salt-sensitive, as manifested by a rise in blood pressure with salt loading. We conducted a two-stage genetic analysis in hypertensive patients very accurately phenotyped for their salt-sensitivity. All newly discovered never treated before, essential hypertensives underwent an acute salt load to monitor the simultaneous changes in blood pressure and renal sodium excretion. The first stage consisted in an association analysis of genotyping data derived from genome-wide array on 329 subjects. Principal Component Analysis demonstrated that this population was homogenous. Among the strongest results, we detected a cluster of SNPs located in the first introns of PRKG1 gene (rs7897633, p = 2.34E-05) associated with variation in diastolic blood pressure after acute salt load. We further focused on two genetic loci, SLC24A3 and SLC8A1 (plasma membrane sodium/calcium exchange proteins, NCKX3 and NCX1, respectively) with a functional relationship with the previous gene and associated to variations in systolic blood pressure (the imputed rs3790261, p = 4.55E-06; and rs434082, p = 4.7E-03). In stage 2, we characterized 159 more patients for the SNPs in PRKG1, SLC24A3 and SLC8A1. Combined analysis showed an epistatic interaction of SNPs in SLC24A3 and SLC8A1 on the pressure-natriuresis (p interaction = 1.55E-04, p model = 3.35E-05), supporting their pathophysiological link in cellular calcium homeostasis. In conclusions, these findings point to a clear association between body sodium-blood pressure relations and molecules modulating the contractile state of vascular cells through an increase in cytoplasmic calcium concentration.
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spelling pubmed-30904072011-05-13 Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension Citterio, Lorena Simonini, Marco Zagato, Laura Salvi, Erika Delli Carpini, Simona Lanzani, Chiara Messaggio, Elisabetta Casamassima, Nunzia Frau, Francesca D'Avila, Francesca Cusi, Daniele Barlassina, Cristina Manunta, Paolo PLoS One Research Article The importance of excess salt intake in the pathogenesis of hypertension is widely recognized. Blood pressure is controlled primarily by salt and water balance because of the infinite gain property of the kidney to rapidly eliminate excess fluid and salt. Up to fifty percent of patients with essential hypertension are salt-sensitive, as manifested by a rise in blood pressure with salt loading. We conducted a two-stage genetic analysis in hypertensive patients very accurately phenotyped for their salt-sensitivity. All newly discovered never treated before, essential hypertensives underwent an acute salt load to monitor the simultaneous changes in blood pressure and renal sodium excretion. The first stage consisted in an association analysis of genotyping data derived from genome-wide array on 329 subjects. Principal Component Analysis demonstrated that this population was homogenous. Among the strongest results, we detected a cluster of SNPs located in the first introns of PRKG1 gene (rs7897633, p = 2.34E-05) associated with variation in diastolic blood pressure after acute salt load. We further focused on two genetic loci, SLC24A3 and SLC8A1 (plasma membrane sodium/calcium exchange proteins, NCKX3 and NCX1, respectively) with a functional relationship with the previous gene and associated to variations in systolic blood pressure (the imputed rs3790261, p = 4.55E-06; and rs434082, p = 4.7E-03). In stage 2, we characterized 159 more patients for the SNPs in PRKG1, SLC24A3 and SLC8A1. Combined analysis showed an epistatic interaction of SNPs in SLC24A3 and SLC8A1 on the pressure-natriuresis (p interaction = 1.55E-04, p model = 3.35E-05), supporting their pathophysiological link in cellular calcium homeostasis. In conclusions, these findings point to a clear association between body sodium-blood pressure relations and molecules modulating the contractile state of vascular cells through an increase in cytoplasmic calcium concentration. Public Library of Science 2011-05-09 /pmc/articles/PMC3090407/ /pubmed/21573014 http://dx.doi.org/10.1371/journal.pone.0019620 Text en Citterio et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Citterio, Lorena
Simonini, Marco
Zagato, Laura
Salvi, Erika
Delli Carpini, Simona
Lanzani, Chiara
Messaggio, Elisabetta
Casamassima, Nunzia
Frau, Francesca
D'Avila, Francesca
Cusi, Daniele
Barlassina, Cristina
Manunta, Paolo
Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension
title Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension
title_full Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension
title_fullStr Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension
title_full_unstemmed Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension
title_short Genes Involved in Vasoconstriction and Vasodilation System Affect Salt-Sensitive Hypertension
title_sort genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090407/
https://www.ncbi.nlm.nih.gov/pubmed/21573014
http://dx.doi.org/10.1371/journal.pone.0019620
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