[Variant frequency of GJB2 c.109G>A (p.Val37Ile) in Chinese patients with hearing loss: a systematic review and...

Objective: This study aims to systematically evaluate the frequency and geographic distribution of the GJB2 c.109G>A (p.Val37Ile) variant in the Chinese patients with hearing loss, providing a data-driven basis for hereditary hearing loss prevention and control. Methods: A comprehensive literature search was conducted across seven databases-PubMed, Embase, Science Direct, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang Data System-from their inception to May 31, 2025. Studies were screened based on predefined inclusion and exclusion criteria. Data analysis was performed using R 4.4.2. Meta-analysis was applied to calculate the variant carrier rate, allele frequency, and corresponding 95% confidence intervals of GJB2 c.109G>A (p.Val37Ile). Funnel plots and Egger's test were employed to assess publication bias. Results: A total of 53 studies were included, covering 28 430 individuals with hearing loss across 17 provinces in China. Meta-analysis showed that the overall carrier rate of the GJB2 c.109G>A (p.Val37Ile) variant was 11.2% (95%CI: 8.8%-13.7%), and the allele frequency was 6.7% (95%CI: 5.0%-8.3%) in the Chinese patients with hearing loss. Subgroup analysis found that the variant frequency in southern China was significantly higher than in northern China (P<0.05). The carrier rate in southern Chinese was 16.0% (95%CI: 12.3%-19.8%),that with an allele frequency of 10.5% (95%CI: 7.5%-13.4%). In northern China, the carrier rate was 3.4% (95%CI: 2.5%-4.3%), with an allele frequency of 2.0% (95%CI: 1.5%-2.6%). Conclusions: The GJB2 c.109G>A (p.Val37Ile) variant exhibits a relatively high carrier rate and allele frequency among the Chinese patients with hearing loss, with a significant regional distribution pattern from south to north. This finding not only provides an important reference for genetic screening and counseling of hearing loss, but also offers evidence-based support for developing regional hearing health strategies.