Functional BSND Variants in Essential Hypertension
Oxford University Press, 2007
Online
academicJournal
Zugriff:
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. Am J Hypertens 2007;20: 1176–1182 © 2007 American Journal of Hypertension, Ltd.
Titel: |
Functional BSND Variants in Essential Hypertension
|
---|---|
Autor/in / Beteiligte Person: | Sile, Saba ; Gillani, Niloufar B. ; Velez, Digna R. ; Vanoye, Carlos G. ; Yu, Chang ; Byrne, Loretta M. ; Gainer, James V. ; Brown, Nancy J. ; Williams, Scott M. ; George, Alfred L. |
Link: | |
Veröffentlichung: | Oxford University Press, 2007 |
Medientyp: | academicJournal |
DOI: | 10.1016/j.amjhyper.2007.07.003 |
Schlagwort: |
|
Sonstiges: |
|