ArticleOtology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology2026
Genotype-guided Recall Delineates the Adult Auditory Phenotype in GJB2 p.V37I Homozygotes: High-frequency Vulnerability and Environmental Modulation.
Article in Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGJB2 p.V37I is common in East Asian populations and is an established contributor to mild-to-moderate hearing loss, yet the adult auditory phenotype and its modification by environmental exposures remain incompletely defined.
methodsWe conducted a genotype-guided case-control recall study within the Taiwan Precision Medicine Initiative, enrolling 191 adults (96 p.V37I homozygotes; 95 genotype-negative controls). Participants received pure-tone audiometry (0.25-8 kHz) and tinnitus assessment (THI-CM), with cardiometabolic and lifetime noise-exposure ascertainment. Abnormal hearing was defined as PTA (0.5, 1, 2, 4 kHz) ≥16 dB HL; clinically significant tinnitus handicap as THI-CM ≥18.
resultsHomozygotes showed bilateral, symmetric, high-frequency-predominant threshold elevation (4-8 kHz). Abnormal hearing was more frequent in homozygotes than controls (right 84.4% vs. 16.8%; left 80.2% vs. 16.8%). In adjusted models, homozygosity remained independently associated with abnormal hearing (right aOR 7.57, 95% CI: 2.77-20.67; left aOR 6.52, 95% CI: 2.52-16.86), together with age (right aOR 1.08/year; left aOR 1.05/year). Noise exposure showed strong univariate associations but was attenuated after adjustment. Clinically significant tinnitus handicap (17.7% vs. 5.3%) and dizziness (26.0% vs. 8.4%) were more frequent in homozygotes; however, tinnitus was independently associated with noise exposure ( aOR 4.30, 95% CI: 1.41-13.08) but not genotype.
conclusionsGenotype-guided recall delineates a clinically recognizable adult p.V37I audiometric phenotype marked by symmetric, high-frequency-predominant threshold elevation with age-dependent expression, supporting phenotype-guided counseling and longitudinal surveillance.
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