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Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

ABSTRACT: Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC), thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity.39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques.Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR) (18.0, 7.5-20.0 mmHg vs 6.0, 0.0-10.0 mmHg, P = 0.007) and lower plasma renin concentration (P-renin) (6.0, 2.0-9.5 mU/L vs 15.0, 9.0-24.0 mU/L, P = 0.005) as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0-18.0 mmHg vs 5.0, 0.0-10.0 mmHg, P = 0.07) and P-renin (9.0, 6.0-16.0 mU/L vs 15.0, 9.0-28.0 mU/L, P = 0.03).Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension.

SUBMITTER: Dahlberg J

PROVIDER: S-EPMC1855992 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

Dahlberg Jonas J Nilsson Lars-Olof LO von Wowern Fredrik F Melander Olle O

PloS one 20070509 5

<h4>Objective</h4>Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L) is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC), thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A) GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T) polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is assoc ...[more]

PMID: 17487281

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Project description:Background Enlargement of left atrial ( LA ) size indicates advanced disease stage in patients with atrial fibrillation ( AF ) and is associated with poor success of different AF therapies. Two dimensional echocardiographic LA measurements do not reliably reflect the true size of LA anatomy. The aim of the current study was: 1) to analyze cardiovascular magnetic resonance ( CMR )-derived LA dimensions and their association with low voltage areas ( LVA ); and 2) to investigate the association between these parameters and NT -pro ANP (N-terminal proatrial natriuretic peptide) levels. Methods and Results Patients undergoing first AF catheter ablation were included. All patients underwent CMR imaging (Ingenia 1.5T Philips) before intervention. CMR data ( LA volume, superior-inferior, transversal and anterior-posterior LA diameters) were measured in all patients. LVA were determined using high-density maps and a low voltage threshold <0.5 mV. Blood plasma samples from femoral vein were collected before catheter ablation. NT -pro ANP levels were studied using commercially available assays. There were 216 patients (65±11 years, 59% males, 56% persistent AF , 26% LVA ) included into analyses. NT -pro ANP levels in patients with LVA were significantly higher than in those without (median/interquartile range 22 [13-29] versus 15 [9-22] pg/mL, P=0.004). All CMR derived LA diameters correlated significantly with persistent AF ( r²=0.291-0.468, all P<0.001), LVA ( r²=0.187-0.306, all P<0.001), and NT -pro ANP levels ( r²=0.258-0.352, P<0.01). On logistic regression multivariable analysis, age (odds ratio=1.090, 95% confidence interval: 1.030-1.153, P=0.003), females (odds ratio=2.686, 95% confidence interval: 1.047-6.891, P=0.040), and LA volume (odds ratio=1.022, 95% confidence interval: 1.009-1.035, P=0.001) remained significant predictors for LVA . Conclusions Left atrial CMR parameters are associated with persistent AF , low voltage areas and NT -pro ANP levels. LA volume is the most significant predictor for LVA .

Dataset Information

Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

Publications

Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

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