Downregulation of VDR in benign paroxysmal positional vertigo patients inhibits otolith‑associated protein expression levels

Abstract

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vertigo‑associated disease. Vitamin D (VD) helps maintain normal otolith function and may be associated with BPPV. VD exerts its biological functions primarily via the VD receptor (VDR). The present study demonstrated that serum VD levels were significantly decreased in patients with BPPV compared with in controls. VDR, otolith‑associated protein otoconin‑90 (OC90) and NADPH oxidase 3 (NOX3) expression levels were also significantly decreased in patients with BPPV compared with in controls. Furthermore, a positive correlation was observed between VD levels and VDR expression. Receiver operating characteristic curve analysis identified VDR expression levels as a potential diagnostic marker for BPPV. OC90 and NOX3 expression levels were notably lower in the inner ear tissue of VDR knockout mice compared with in those of wild‑type mice. In mice overexpressing VDR, OC90 and NOX3 were also overexpressed. Following intravenous injection of VD in VDR knockout mice, expression levels of OC90 and NOX3 were not significantly different from those in VDR knockout mice injected with saline. This indicated that VDR may be underexpressed in patients with BPPV and was associated with the expression levels of otolith‑associated proteins. Moreover, VDR mediated VD activation, leading to otolith protein formation. The present study provided a novel theoretical basis for BPPV onset that may facilitate the development of more effective diagnostic and treatment options.

Keywords: benign paroxysmal positional vertigo; inner ear; vitamin D; vitamin D receptor.