Functional <italic>BSND</italic> Variants in Essential Hypertension<xref ref-type="author-notes" rid="fn1">^*</xref><subtitle />

• DOI: 10.1016/j.amjhyper.2007.07.003
• Publication Date: 2017-05-09T18:53:41Z
• Authors: Digna R. Velez; Scott M. Williams; Alfred L. George; Saba Sile; Niloufar B. Gillani; Loretta M. Byrne; James V. Gainer; Chang Yu; Nancy J. Brown; Carlos G. Vanoye
• Keywords: 0303 health sciences; Polymorphism, Genetic; Population; Genetic Variation; Membrane Proteins; DNA; Ghana; Cohort Studies; Electrophysiology; 03 medical and health sciences; Logistic Models; Gene Frequency; Chloride Channels; Hypertension; Ethnicity; Odds Ratio; Humans; Alleles; Polymorphism, Single-Stranded Conformational

Defects in the handling of renal salt reabsorption may contribute to interindividual differences in blood-pressure regulation and susceptibility to hypertension. Sodium chloride reabsorption in the thick ascending limb (TAL) is dependent in part on the chloride channel, ClC-Kb (encoded by CLCNKB), and its accessory subunit, barttin (encoded by BSND).We investigated genetic variations in BSND in a screening population, and genotyped a homogenous cohort of normotensive and hypertensive Ghanaian subjects, in addition to four ethnically defined control populations. Functional consequences of the identified BSND variants were examined using a heterologous expression system.Three novel, nonsynonymous coding-sequence single-nucleotide polymorphisms were identified (V43I, E255Q, and G284D) in the screening population. BSND-V43I was identified in African American, Asian, and Hispanic subjects, with minor allele frequencies of 0.14, 0.18, and 0.01, respectively, but it was absent in the Caucasian population. BSND-E225Q and BSND-G284D were rare variants. Two of these variants (V43I and G284D) exhibited partial loss-of-function phenotypes when heterologously expressed with ClC-Kb chloride channels in cultured cells. In logistic regression analyses, we observed no association between hypertension and BSND-I43 in our study population. However, we did observe significant deviation from Hardy-Weinberg equilibrium in the normotensive population.We conclude that BSND-V43I, a common variant conferring partial loss of function, exhibits significant deviation from Hardy-Weinberg equilibrium in the Ghanaian normotensive control population. However, it does not independently confer protection against hypertension.