# Association of sleep quality and inner-ear–specific biomarkers Otolin-1 and otoconin-90 with disease severity in benign paroxysmal positional vertigo

## TL;DR

Poor sleep quality and higher levels of inner-ear biomarkers are linked to more severe vertigo symptoms in BPPV patients.

## Contribution

This study identifies inner-ear biomarkers Otolin-1 and otoconin-90 as novel indicators of BPPV severity and sleep-related symptom associations.

## Key findings

- BPPV patients had significantly higher serum levels of Otolin-1 and otoconin-90 compared to healthy controls.
- Poorer sleep quality was associated with increased vertigo severity and higher biomarker levels.
- Biomarkers partially explain the relationship between sleep quality and vertigo symptoms in BPPV.

## Abstract

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder and exhibits marked heterogeneity in symptom burden and clinical course. Objective biomarkers reflecting inner-ear structural status and their relationship with clinical manifestations remain limited. Emerging evidence suggests an association between sleep quality and vertigo symptoms; however, the biological basis underlying this relationship is poorly understood.

In this case–control study, 268 patients with BPPV and 268 age- and sex-matched healthy controls were enrolled. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and vertigo severity was evaluated using the Dizziness Handicap Inventory (DHI). Serum levels of the inner-ear–specific structural biomarkers Otolin-1 and otoconin-90 (OC90) were measured using enzyme-linked immunosorbent assays. Logistic regression was used to examine associations with BPPV presence. Among patients with BPPV, multivariable linear regression, joint models, and exploratory mediation analyses were conducted to evaluate relationships among sleep quality, biomarkers, and symptom severity.

Compared with healthy controls, patients with BPPV exhibited significantly higher serum levels of the inner-ear structural biomarkers Otolin-1 (median 6.38 vs. 3.94 ng/mL) and otoconin-90 (median 12.64 vs. 7.58 ng/mL), both of which were independently associated with the odds of BPPV (adjusted OR for Otolin-1: 2.08, 95% CI: 1.49–2.91; adjusted OR for otoconin-90: 1.71, 95% CI: 1.21–2.42). Among patients with BPPV, poorer sleep quality was associated with greater vertigo severity (β = 2.14 per PSQI point, 95% CI: 1.56–2.72). Higher PSQI scores were also associated with increased levels of Otolin-1 and otoconin-90, both of which were independently related to vertigo severity. Inclusion of these biomarkers in joint models attenuated the PSQI–DHI association (β from 2.14 to 1.28) and improved model explanatory power (R2 from 0.26 to 0.38). Exploratory mediation analyses suggested that Otolin-1 and otoconin-90 statistically accounted for approximately 40 and 29% of the sleep–symptom association, respectively, with consistent findings across sensitivity and subgroup analyses.

These findings indicate that otolith-related inner-ear structural biomarkers are associated with both the presence and severity of BPPV and may partially explain the relationship between sleep quality and vertigo symptoms.