| The functional c.-2G>C variant of the mineralocorticoid receptor modulates blood pressure, renin, and aldosterone levels. | |
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MedLine Citation:
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PMID: 20855654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mineralocorticoid receptor (MR) is essential in the regulation of volemia and blood pressure. Rare mutations in the MR gene cause type 1 pseudohypoaldosteronism and hypertension. In this study we characterized the common MR polymorphism c.-2G>C (rs2070951) in vitro and tested its influence on parameters related to blood pressure regulation and the renin-angiotensin system. In vitro studies showed that the G allele was associated with decreased MR protein levels and reduced transcriptional activation compared with the C allele. Association studies were performed with several outcome variables in 3 independent cohorts: a mild hypertensive group subjected to a salt-sensitivity test, a healthy normotensive group included in a crossover study to receive both a high and low Na/K diet, and a large cohort (The Netherlands Study of Depression and Anxiety), in which blood pressure was measured. Subjects with the GG genotype had significantly higher plasma renin levels both in the mild hypertensive group and in normal volunteers compared with homozygous C carriers. The GG genotype was also correlated with higher plasma aldosterone levels in healthy subjects. In both the mild hypertensive group and The Netherlands Study of Depression and Anxiety cohort the genotype GG was associated with higher systolic blood pressure in males. In conclusion, the G allele of the common functional genetic polymorphism c.-2G>C in the MR gene associates with increased activation of the renin-angiotensin-aldosterone axis and with increased blood pressure, probably related to decreased MR expression. |
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Authors:
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Nienke van Leeuwen; Massimiliano Caprio; Carolina Blaya; Frédéric Fumeron; Paola Sartorato; Vanessa Ronconi; Gilberta Giacchetti; Franco Mantero; Fabio L Fernandes-Rosa; Christophe Simian; Sévrine Peyrard; Frans G Zitman; Brenda W J H Penninx; E Ron de Kloet; Michel Azizi; Xavier Jeunemaitre; Roel H Derijk; Maria-Christina Zennaro |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-20 |
Journal Detail:
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Title: Hypertension Volume: 56 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-21 Completed Date: 2010-11-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 995-1002 Citation Subset: IM |
Affiliation:
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Division of Medical Pharmacology/Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aldosterone / blood*, genetics Alleles Blood Pressure / genetics* Cross-Over Studies Female Genetic Association Studies Genotype Humans Male Middle Aged Polymorphism, Single Nucleotide Receptors, Mineralocorticoid / genetics* Renin / blood*, genetics Renin-Angiotensin System / genetics* Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Mineralocorticoid; 52-39-1/Aldosterone; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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