Variant frequency of GJB2 c.109G>A (p.Val37Ile) in the general Chinese population: A systematic review and meta-analysis

This study systematically evaluates the frequency and geographic distribution of the GJB2 c.109G > A (p.Val37Ile) variant in the Chinese population, providing a data-driven basis for hereditary hearing loss prevention and control.

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 through 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. Funnel plots and Egger's test were employed to assess publication bias.

A total of 37 studies were included, encompassing 364,088 individuals across 18 provinces in China. Meta-analysis indicated that the overall carrier rate of the GJB2 c.109G > A variant was 11.6 % (95 % CI: 9.5 %-14.1 %), and the allele frequency was 6.3 % (95 % CI: 5.2 %-7.7 %). Stratified analysis revealed that both the carrier rate (14.5 %, 95 % CI: 12.4 %-17.0 %) and allele frequency (8.1 %, 95 % CI: 7.0 %-9.3 %) were considerably higher in southern Chinese populations compared to northern regions (carrier rate 5.3 %, 95 % CI: 4.0 %-6.9 %; allele frequency 2.7 %, 95 % CI: 2.2 %-3.3 %), with statistically significant differences (P < 0.05).

The GJB2 c.109G > A (p.Val37Ile) variant exhibits a relatively high carrier rate and allele frequency within the general Chinese population, with significant regional variation. These findings offer valuable insights for genetic counseling, disease prevention, and hearing health policy, and they highlight the need to account for regional and ethnic diversity in genetic studies.