ArticleOtolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery2026
Association of GJB2 P.V37I With Sudden Sensorineural Hearing Loss and Endoplasmic Reticulum Stress.
Article in Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 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
objectiveThis study aimed to investigate the association between the heterozygous GJB2 p.V37I variant and susceptibility to sudden sensorineural hearing loss (SSNHL), and to explore its potential involvement in endoplasmic reticulum (ER) stress. STUDY
designGenetic association study with in vitro functional validation.
settingTertiary academic medical center.
methodsWe screened 145 SSNHL patients for 25 variants in GJB2, SLC26A4, OTOF, and 12S rRNA using the SNaPshot® Multiplex Assay. GJB2 p.V37I frequency was compared with the Taiwan Biobank, and associations with hearing severity and recurrence were analyzed. Functional studies in HEI-OC1 cells transfected with wild-type or p.V37I GJB2 assessed ER stress (GRP78, CHOP) under tunicamycin by Western blot and immunofluorescence.
resultsThe GJB2 p.V37I variant was identified in 39/145 SSNHL patients (26.9%) and showed significant allele enrichment compared with the general Taiwanese population (8.6%; enrichment OR = 1.92; P < .001), suggesting a genetic susceptibility contribution. The variant was associated with a higher prevalence of moderate (OR, 1.94; P = .019) and severe (OR, 1.90; P = .013) SSNHL, as well as recurrent episodes (OR, 3.77; P = .008). In vitro, p.V37I-expressing HEI-OC1 cells, a mouse cochlear hair cell line, showed significantly elevated GRP78 and CHOP expression compared to wild-type under tunicamycin induced ER stress, as confirmed by both immunoblotting and immunofluorescence microscopy.
conclusionOur findings indicate that the heterozygous GJB2 p.V37I variant is associated with increased susceptibility and recurrence of SSNHL, potentially through ER stress-related mechanisms, supporting genetic screening and further mechanistic studies.
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