Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_2C99E72EB832
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension.
Périodique
BMC Medical Genetics
Auteur(s)
Hannila-Handelberg T., Kontula K., Tikkanen I., Tikkanen T., Fyhrquist F., Helin K., Fodstad H., Piippo K., Miettinen H.E., Virtamo J., Krusius T., Sarna S., Gautschi I., Schild L., Hiltunen T.P.
ISSN
1471-2350
Statut éditorial
Publié
Date de publication
01/2005
Peer-reviewed
Oui
Volume
6
Pages
4
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
BACKGROUND: Rare mutations of the epithelial sodium channel (ENaC) result in the monogenic hypertension form of Liddle's syndrome. We decided to screen for common variants in the ENaC beta and gamma subunits in patients with essential hypertension and to relate their occurrence to the activity of circulating renin-angiotensin-aldosterone system. METHODS: Initially, DNA samples from 27 patients with low renin/low aldosterone hypertension were examined. The DNA variants were subsequently screened for in 347 patients with treatment-resistant hypertension, 175 male subjects with documented long-lasting normotension and 301 healthy Plasma renin and aldosterone levels were measured under baseline conditions and during postural and captopril challenge tests. RESULTS: Two commonly occurring betaENaC variants (G589S and a novel intronic i12-17CT substitution) and one novel gammaENaC variant (V546I) were detected. One of these variants occurred in a heterozygous form in 32 patients, a prevalence (9.2%) significantly higher than that in normotensive males (2.9%, p = 0.007) and blood donors (3.0%, p = 0.001). betaENaC i12-17CT was significantly more prevalent in the hypertension group than in the two control groups combined (4.6% vs. 1.1%, p = 0.001). When expressed in Xenopus oocytes, neither of the two ENaC amino acid-changing variants showed a significant difference in activity compared with ENaC wild-type. No direct evidence for a mRNA splicing defect could be obtained for the betaENaC intronic variant. The ratio of daily urinary potassium excretion to upright and mean (of supine and upright values) plasma renin activity was higher in variant allele carriers than in non-carriers (p = 0.034 and p = 0.048). CONCLUSIONS: At least 9% of Finnish patients with hypertension admitted to a specialized center carry genetic variants of beta and gammaENaC, a three times higher prevalence than in the normotensive individuals or in random healthy controls. Patients with the variant alleles showed an increased urinary potassium excretion rate in relation to their renin levels.
Mots-clé
Adult, Aged, Aldosterone, Alleles, Epithelial Sodium Channel, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Hypertension, Male, Middle Aged, Protein Subunits, Renin, Renin-Angiotensin System, Sequence Analysis, DNA, Sodium Channels
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:56
Dernière modification de la notice
20/08/2019 14:11
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