title: Functional BSND variants in essential hypertension.
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.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-0275, USA. saba.sile@vanderbilt.edu
authors.forename: Saba
authors.initials: S
authors.lastname: Sile
authors.forename: Niloufar B
authors.initials: NB
authors.lastname: Gillani
authors.forename: Digna R
authors.initials: DR
authors.lastname: Velez
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Vanoye
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: Loretta M
authors.initials: LM
authors.lastname: Byrne
authors.forename: James V
authors.initials: JV
authors.lastname: Gainer
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: Alfred L
authors.initials: AL
authors.lastname: George
mesh_terms: D000483:Alleles; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004594:Electrophysiology; D005006:Ethnicity; D005787:Gene Frequency; D014644:Genetic Variation; D005869:Ghana / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D016015:Logistic Models; D008565:Membrane Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011153:Population
chemical_list: C440005:BSND protein, human; D018118:Chloride Channels; D008565:Membrane Proteins; D004247:DNA