Serum Levels of Prestin, Otoferlin, Connexin 26, and Stereocilin: A Biomarker Approach to Tinnitus

OBJECTIVE: Tinnitus is a prevalent auditory disorder lacking objective diagnostic tools. An outer hair cell (OHC) protein, prestin, has been implicated in the pathophysiology of tinnitus. This study adopts a biomarker approach by quantifying serum levels of prestin, as well as functionally important inner ear proteins, otoferlin, connexin 26 (CX26), and stereocilin in individuals with and without tinnitus, to test the hypothesis that prestin plays a role in tinnitus. STUDY DESIGN: Observational cohort study. SETTING: Tertiary academic center. METHODS: In all, 82 participants (41 with chronic, bilateral, non-pulsatile tinnitus and 41 controls) underwent audiometry, 1-week personal noise dosimetry, Tinnitus Handicap Inventory (THI) assessment, and venipuncture. Serum concentrations of the four cochlear proteins were quantified via enzyme-linked immunosorbent assays. Statistical analyses included multivariate Quade ANCOVA to account for age, hearing thresholds, and daily noise exposure. RESULTS: Serum prestin levels were significantly higher in tinnitus subjects compared to controls (P = .006), and this difference remained significant after controlling for key covariates, noise, hearing loss, and age (P = .003). No significant group differences were found for otoferlin, CX26, or stereocilin. Prestin and stereocilin levels were positively correlated across subjects (ρ = .51, P < .001), with stronger correlations observed in the Tinnitus group. CX26 and stereocilin levels correlated with age and hearing thresholds but did not distinguish tinnitus status. No protein levels correlated with THI scores. CONCLUSION: Prestin, but not other protein levels, were elevated in tinnitus subjects, supporting a role for the OHCs in the pathophysiology of tinnitus. Other inner ear proteins may have a role as biomarkers of cochlear health.