scholarly journals Plasma potassium level is associated with common genetic variation in the β-subunit of the epithelial sodium channel

2008 ◽  
Vol 294 (3) ◽  
pp. R1068-R1072 ◽  
Author(s):  
Nicole Gaukrodger ◽  
Peter J. Avery ◽  
Bernard Keavney
Keyword(s):  
Blood Pressure ◽  
Genetic Variation ◽  
Sodium Channel ◽  
Venous Blood ◽  
Ambulatory Monitoring ◽  
Blood Pressure Level ◽  
Plasma Potassium ◽  
Epithelial Sodium Channel ◽  
Β Subunit ◽  
Common Genetic Variation

Plasma potassium is a moderately heritable phenotype, but no robust associations between common single nucleotide polymorphisms (SNPs) and plasma potassium have previously been described. Genetic influences on renal potassium handling could be important in the etiology of hypertension. We have tested whether common genetic variation in the gene encoding the β-subunit of the epithelial sodium channel (SCNN1B) affects plasma potassium and blood pressure level in a study of 1,425 members of 248 families ascertained on a proband with hypertension. We characterized family members for blood pressure using ambulatory monitoring, measured plasma potassium in venous blood samples, and genotyped four SNPs that spanned the SCNN1B gene. We found highly significant association between genotype at the SCNN1B rs889299 SNP situated in intron 4 of the gene and plasma potassium. Homozygotes for the rarer T allele had on average a 0.15 mM lower plasma potassium than homozygotes for the common C allele, with an intermediate value for heterozygotes (trend, P = 0.0003). Genotype at rs889299 accounted for ∼1% of the total variability in plasma potassium, or around 3% of the total heritable fraction. There was no association between genotype at any SCNN1B SNP and blood pressure considered as a quantitative trait, or with hypertension affection status. We have shown a modest sized but highly significant effect of common genetic variation in the SCNN1B gene on plasma potassium. Interaction between the rs889299 SNP and functional SNPs in other genes influencing aldosterone-responsive distal tubular electrolyte transport may be important in the etiology of essential hypertension.

A novel frameshift mutation of epithelial sodium channel β-subunit leads to Liddle syndrome in an isolated case

2015 ◽  
Vol 82 (4) ◽  
pp. 611-614 ◽  
Author(s):  
Kun-Qi Yang ◽  
Chao-Xia Lu ◽  
Yan Xiao ◽  
Ya-Xin Liu ◽  
Xiong-Jing Jiang ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Frameshift Mutation ◽  
Epithelial Sodium Channel ◽  
Β Subunit ◽  
Liddle Syndrome

Differential Regulation of the Epithelial Sodium Channel (ENaC) in Rat Kidney, Lung and Distal Colon in Response to Aldosterone.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 724-724
Author(s):  
Shyama M E Masilamani ◽  
Gheun-Ho Kim ◽  
Mark A Knepper
Keyword(s):  
Sodium Channel ◽  
Epithelial Sodium Channel ◽  
Distal Colon ◽  
Β Subunit ◽  
Dietary Salt ◽  
Α Subunit ◽  
Salt Restriction ◽  
Γ Subunit ◽  
Dietary Salt Restriction ◽  
Epithelial Sodium Channel Enac

P170 The mineralocorticoid hormone, aldosterone increases renal tubule Na absorption via increases in the protein abundances of the α-subunit of the epithelial sodium channel (ENaC) and the 70 kDa form of the γ- subunit of ENaC (JCI 104:R19-R23). This study assesses the affect of dietary salt restriction on the regulation of the epithelial sodium channel (ENaC) in the lung and distal colon, in addition to kidney, using semiquantitative immunoblotting. Rats were placed initially on either a control Na intake (0.02 meq/day), or a low Na intake (0.2 meq/day) for 10 days. The low salt treated rats demonstrated an increase in plasma aldosterone levels at day 10 (control = 0.78 + 0.32 nM; Na restricted = 3.50 + 1.30 nM). In kidney homogenates, there were marked increases in the band density of the α-subunit of ENaC (286 % of control) and the 70 kDa form of γ-subunit of ENaC (262 % of control), but no increase in the abundance of the β-subunit of ENaC. In lung homogenates, there was no significant change in the band densities of the α, β, or γ subunits of ENaC. In distal colon, there was an increase in the band density of the β-subunit of ENaC (311 % of control) and an increase in both the 85 kDa (2355% of control) and 70 kDa (843 % of control) form of the γ subunit of ENaC in response to dietary Na restriction. However, there was no significant difference in the band density of the α-subunit of ENaC. These findings demonstrate tissue specific regulation of the three subunits of ENaC in response to dietary salt restriction.

Abstract P262: Resequencing Study Identifies Epithelial Sodium Channel Genes and Novel Low Frequency Variants Associated with Blood Pressure Salt-sensitivity: The GenSalt Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Christopher E Anderson ◽  
Changwei Li ◽  
Jiang He ◽  
Dongfeng Gu ◽  
Dabeeru C Rao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Family Structure ◽  
Sodium Channel ◽  
Association Studies ◽  
Low Frequency ◽  
Epithelial Sodium Channel ◽  
Salt Sensitivity ◽  
Minor Allele ◽  
Indicator Variable ◽  
High Sodium

Christopher E. Anderson, Changwei Li, Jiang He, Dongfeng Gu, Dabeeru C. Rao, James E. Hixson, Lawrence C. Shimmin, Jianfeng Huang, Charles C. Gu, Jichun Chen, Jianxin Li, Tanika N. Kelly Genetic association studies have identified significant associations between common variants from the epithelial sodium channel (ENaC) genes and blood pressure responses to dietary sodium interventions. The roles of low-frequency and rare ENaC variants in blood pressure salt-sensitivity remain largely unexplored. To test this hypothesis, we conducted an ENaC candidate gene resequencing study among participants in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt). The GenSalt study was conducted among 1,906 participants from 633 families who underwent a 7-day low-sodium (51.3 mmol sodium/day) followed by a 7-day high-sodium (307.8 mmol sodium/day) feeding-study. We chose the 300 GenSalt subjects with the highest and 300 GenSalt subjects with the lowest mean arterial pressure responses to the high sodium intervention to participate in the current resequencing study. Functional regions of three ENaC subunit genes ( SCNN1A , SCNN1B and SCNN1G ) were resequenced using the VariantSEQr TM system (Applied Biosystems; Foster City, CA). For gene-based analyses, variants with MAF less than 5% were first collapsed within each ENaC gene. The collapsed indicator variable was then tested for association with blood pressure salt-sensitivity using generalized estimating equations (GEE) to accommodate correlation of genotypes due to family structure and adjust for the fixed effects of age, gender and field center. Single variant analyses were performed for all low-frequency variants with a minor allele frequency (MAF) greater than 1% and less than 5%, again using GEE to accommodate family structure and adjust for covariables. We did not identify any associations between ENaC genes and blood pressure salt-sensitivity in the gene-based analyses. However, single variant analysis identified a novel association between a low-frequency variant in SCNN1G , rs148083677, and blood pressure salt-sensitivity (P=0.02). Each minor allele was associated with 71% lower odds of blood pressure salt-sensitivity. Although replication studies are needed, these findings provide promising evidence of a role for low-frequency ENaC variants in blood pressure salt-sensitivity.

scholarly journals (Pro)Renin receptor mediates obesity-induced antinatriuresis and elevated blood pressure via upregulation of the renal epithelial sodium channel

PLoS ONE ◽  
2018 ◽  
Vol 13 (8) ◽  
pp. e0202419 ◽  
Author(s):  
Syed S. Quadri ◽  
Silas Culver ◽  
Nrupama Ramkumar ◽  
Donald E. Kohan ◽  
Helmy M. Siragy
Keyword(s):  
Blood Pressure ◽  
Sodium Channel ◽  
Epithelial Sodium Channel ◽  
Elevated Blood Pressure ◽  
Elevated Blood
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