Human Epithelial Na+ Channel Missense Variants Identified in the GenSalt Study Alter Channel Activity.

This study sought to identify functional human ENaC variants, to examine how these variants alter channel activity, and to explore whether these variants are associated with altered sensitivity of blood pressure to dietary salt. Six-hundred participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study with salt-sensitive or salt-resistant blood pressure underwent sequencing of the genes encoding ENaC subunits. Functional effects of identified variants were examined in a Xenopus oocyte expression system. Variants that increased channel activity included three in the gene encoding the α subunit (αS115N, αR476W and αV481M), one in the β subunit (βS635N), and one in the γ subunit (γL438Q). One α subunit variant (αA334T) and one β subunit variant (βD31N) decreased channel activity. Several α subunit extracellular domain variants altered channel inhibition by extracellular Na(+) (Na(+) self-inhibition). One variant (αA334T) decreased and one (αV481M) increased cell-surface expression. Association between these variants and salt-sensitivity did not reach statistical significance. This study identifies novel, functional human ENaC variants and demonstrates that some variants alter channel cell surface expression and/or Na(+) self-inhibition. PMID: 27582106 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research