Research of the rs11064153 variant of the SCNN1A gene in patients with arterial hypertension and in healthy people in the Trans-Baikal

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Abstract

The aim of the study was to evaluate the putative association of the rs11064153 variant of the SCNN1A sodium channel gene with arterial hypertension (AH) among patients suffering from AH and relatively healthy people in the Trans-Baikal Territory.

Design and methods. The present study included 106 patients with a confirmed diagnosis of AH. All participants were included in the study after signing informed consent. The control group consisted of 98 practically healthy people. The groups were comparable in age: the average age in the group with primary AH was 45 ± 9,7 years, in the control group— 42,5 ± 5,8 years. The number of men in group 1 was 73,6% (78/106), in group 2–55,1% (54/98) of the total number of cases (Chi-square = 7,62, df = 1, p < 0,005). Molecular genetics typing of the studied genes was carried out. SNPs of the sodium channel genes SCNN1A (rs11064153) were determined by real-time polymerase chain reaction. We have evaluated the subordination of the distribution of genotypes of samples to the Hardy-Weinberg equilibrium, χ ² -test, and also estimated the odds ratio (OR).

Results. Carriage of the T/T genotype in the group of patients with AH was more frequent than in the control group (97,4% and 86,6%, respectively; χ ² = 8,60, p = 0,01). Thus, carriage of the T/T genotype of the SCNN1A gene increased the likelihood of AH in patients (OR = 2,27, 95% confidence interval (CI) 1,29–4,01, p = 0,01). Among patients, the T allele was detected 1,5 times more often with a frequency of 0,78 compared with the group of healthy individuals — 0,22 (χ ² = 7,28; p = 0,007). The C/C genotype was detected only in three patients from the AH group (2,8%) and in seven patients from the control group (7,1%). It was found that the C allele of the SCNN1А gene (rs11064153) 5 times less often than in the control group, and its frequency was 0,22 versus 0,34, respectively (χ ² = 7,28, p = 0,007). The carriage of the C allele (C/C+T/C genotypes) is associated with a lower incidence in patients with AH (OR = 0.54; 95% CI 0,35–0,85, p = 0,007). In the samples examined by us, the carriage of the C allele reduced the likelihood of AH by 2,3 times.

Conclusions. We have found that the T allele and the T/T genotype of the rs11064153 variant of the SCNN 1A gene increase the likelihood of developing hypertension. Carrying allele C and the C/C SCNN1A genotype (rs11064153) reduces the likelihood of developing AH.

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Most cited references 18

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Israel Hanukoglu, Aaron Hanukoglu (2016)

The epithelial sodium channel (ENaC) is composed of three homologous subunits and allows the flow of Na(+) ions across high resistance epithelia, maintaining body salt and water homeostasis. ENaC dependent reabsorption of Na(+) in the kidney tubules regulates extracellular fluid (ECF) volume and blood pressure by modulating osmolarity. In multi-ciliated cells, ENaC is located in cilia and plays an essential role in the regulation of epithelial surface liquid volume necessary for cilial transport of mucus and gametes in the respiratory and reproductive tracts respectively. The subunits that form ENaC (named as alpha, beta, gamma and delta, encoded by genes SCNN1A, SCNN1B, SCNN1G, and SCNN1D) are members of the ENaC/Degenerin superfamily. The earliest appearance of ENaC orthologs is in the genomes of the most ancient vertebrate taxon, Cyclostomata (jawless vertebrates) including lampreys, followed by earliest representatives of Gnathostomata (jawed vertebrates) including cartilaginous sharks. Among Euteleostomi (bony vertebrates), Actinopterygii (ray finned-fishes) branch has lost ENaC genes. Yet, most animals in the Sarcopterygii (lobe-finned fish) branch including Tetrapoda, amphibians and amniotes (lizards, crocodiles, birds, and mammals), have four ENaC paralogs. We compared the sequences of ENaC orthologs from 20 species and established criteria for the identification of ENaC orthologs and paralogs, and their distinction from other members of the ENaC/Degenerin superfamily, especially ASIC family. Differences between ENaCs and ASICs are summarized in view of their physiological functions and tissue distributions. Structural motifs that are conserved throughout vertebrate ENaCs are highlighted. We also present a comparative overview of the genotype-phenotype relationships in inherited diseases associated with ENaC mutations, including multisystem pseudohypoaldosteronism (PHA1B), Liddle syndrome, cystic fibrosis-like disease and essential hypertension.

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Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.

Stephan Kellenberger, Laurent Schild (2002)

The recently discovered epithelial sodium channel (ENaC)/degenerin (DEG) gene family encodes sodium channels involved in various cell functions in metazoans. Subfamilies found in invertebrates or mammals are functionally distinct. The degenerins in Caenorhabditis elegans participate in mechanotransduction in neuronal cells, FaNaC in snails is a ligand-gated channel activated by neuropeptides, and the Drosophila subfamily is expressed in gonads and neurons. In mammals, ENaC mediates Na+ transport in epithelia and is essential for sodium homeostasis. The ASIC genes encode proton-gated cation channels in both the central and peripheral nervous system that could be involved in pain transduction. This review summarizes the physiological roles of the different channels belonging to this family, their biophysical and pharmacological characteristics, and the emerging knowledge of their molecular structure. Although functionally different, the ENaC/DEG family members share functional domains that are involved in the control of channel activity and in the formation of the pore. The functional heterogeneity among the members of the ENaC/DEG channel family provides a unique opportunity to address the molecular basis of basic channel functions such as activation by ligands, mechanotransduction, ionic selectivity, or block by pharmacological ligands.