Functional BSND Variants in Essential Hypertension

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