Association of Genetic Variation in the Epithelial Sodium Channel Gene with Urinary Sodium Excretion and Blood Pressure

Abstract

This study was performed to investigate whether genetic variation in the epithelial sodium channel (ENaC) is associated with 24-h urinary sodium excretion and blood pressure. A total of 3345 participants of the KoGES_Ansan and Ansung study were eligible for this study. Genomic DNA samples were isolated from peripheral blood and genotyped on the Affymetrix Genome-Wide Human SNP Array 5.0. Thirty-four single nucleotide polymorphisms (SNPs) were extracted for gene regions (SCNN1A, SCNN1B, and SCNN1G) as additive components by using Plink. Twenty-four-hour sodium excretions were estimated from spot urine samples using the Tanaka formula. The general linear model (GLM) was applied to assess the association between SNPs and urinary sodium excretion or blood pressure. In the SCNN1G gene, six SNPs (rs4073291, rs12934362, rs7404408, rs4494543, rs5735, and rs6497657) were significantly different in 24-h urinary sodium excretion according to gene variants. However, no difference was found in blood pressure among participants with gene variants of ENaC. Our finding indicated that 24-h urinary sodium excretions were different according to variants of the SCNN1G gene in large samples. Further studies to replicate these findings are warranted.

Genome-Wide Association Meta-Analysis of Individuals of European Ancestry Identifies Suggestive Loci for Sodium Intake, Potassium Intake, and Their Ratio Measured from 24-Hour or Half-Day Urine Samples

“…One locus for sodium-to-creatinine ratio and 1 locus for potassium-to-creatinine ratio identified by the Zanetti et al (16) GWAS had P < 0.05 with 24-h sodium excretion and 24-h potassium excretion, respectively, in our European ancestry meta-analyses, and the direction of effects was consistent (Supplemental Table 6). Seven out of 9 SNPs in the SCNN1G gene region previously identified by the Yang et al (14) sodium excretion association study (24-h estimated from spot urine samples) or the Zhao et al (18) salt sensitivity of blood pressure in Asian samples association study had GWAS meta-analysis of sodium and potassium intake 2639 The SNPs with strongest P value from each of the genomic risk loci are presented (LD r 2 Age and sex were adjusted in a model.…”

“…We found 2 studies using spot urine samples from the UK Biobank (European ancestry) to examine the concentration (millimoles/liter) of sodium and potassium excretion (15), and sodiumto-creatinine, potassium-to-creatinine, and sodium-to-potassium ratios (16). We also found 2 studies using Asian ancestry samples, one examining 24-h urinary sodium and potassium excretion (mmol/d) estimated from spot urine (14) and the other examining salt sensitivity of blood pressure (18). For the SNPs reported by studies with samples of Asian ancestry, we tested for replication in both our European ancestry samples and our Asian ancestry samples (HTS, Korea).…”

“…However, there has been limited investigation into the specific genetic variants that influence sodium and potassium intake or excretion. Yang et al (14) recently found significant associations of single nucleotide polymorphisms (SNPs) in the epithelial sodium channel gene, sodium channel epithelial 1 subunit gamma (SCNN1G), with 24-h urinary sodium excretion estimated from spot urine samples in a Korean population. Pazoki et al (15) identified 50 loci for the concentrations of sodium excretion and 13 for the concentrations of potassium excretion using spot urine samples in European ancestry UK Biobank data.…”

Electrochemical Label-Free Immunosensor for The Detection of Epithelial Sodium Channels Using Gold Modified Screen-Printed Carbon Electrode

“…That is because a higher number of antibodies can increase the chaos of the antibody attachment arrangement and produce steric obstruction of the immunoreaction. The antibodies immobilized on the surface of the electrode are already saturated so that they interfere with the immobilization process themselves and produce a poor orientation which reduces the number of anti-ENaC antibodies attached to the MPA [13]. According to Ronkainen et al [14], the density or number of antibodies that are immobilized on the surface of the electrode should not be too high because it can cause steric obstruction between antibodies at the electrode which will reduce its recognition activity.…”

Combination of Genome-Wide Polymorphisms and Copy Number Variations of Pharmacogenes in Koreans

“…The Korean genome and epidemiology study (KoGES) is a consortium project that was established as a genome epidemiological study for the research community with a health database and biobank to help investigate Korean population-based and gene–environment model studies [ 26 , 27 , 28 ]. Because this dataset contains a significant collection of SNVs and CNVs data from normal tissue and blood samples, KoGES is appropriate for combined pharmacogenomic studies.…”