Functional BSND Variants in Essential Hypertension

Saba Sile*, Niloufar B. Gillani, Digna R. Velez, Carlos G. Vanoye, Chang Yu, Loretta M. Byrne, James V. Gainer, Nancy J. Brown, Scott M. Williams, Alfred L. George

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1176-1182.e1
JournalAmerican Journal of Hypertension
Volume20
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • BSND
  • hypertension
  • modifier gene
  • protective alleles
  • renal chloride channel

ASJC Scopus subject areas

  • Internal Medicine

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