To assess the association of c. 109G>A (p.V37I) variant of the GJB2 gene and its types with the risk of deafness.

PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database were searched for cases with GJB2 gene c. 109G>A (p.V37I) variant and its compounds with variants of other sites from case-control studies, cohort studies and cross-sectional studies. The search time was from the establishment of database to April 2021. Two researchers have independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and evaluated the included studies according to the criteria. Stata 12.0 software was used for the meta-analysis and publication bias analysis, and a sensitivity analysis was also carried out when necessary.

A total of 22 articles (17 in English and 5 in Chinese) were included. There were 7 455 cases in the deafness group and 10 464 cases in the control group. The results of meta-analysis showed the c. 109G>A (p.V37I) variant to be strongly associated with the risk of deafness (OR: 3.56, 95%CI: 2.31-5.47, P<0.001). Analysis based on the mutational type also suggested c. 109G>A (p.V37I) homozygosity (OR: 11.36, 95%CI: 5.93-21.74, P<0.001) and compound loss of heterozygosity mutations (OR: 9.27, 95%CI: 3.97-21.64, P<0.001) to be strongly associated with the risk of deafness. By contrast, heterozygous c. 109G>A (p.V37I) variant (OR: 1.20, 95%CI: 0.72-2.00, P=0.478) and compound heterozygous missense mutation (OR: 1.54, 95%CI: 0.98-2.44, P=0.063) are not strongly associated with the risk.

The homozygous c. 109G>A (p.V37I) variants of the GJB2 gene and its compound deletional mutation with another GJB2 allele can significantly increase the risk of deafness. Heterozygous c. 109G>A (p.V37I) variant of the GJB2 gene or its compound with a missense mutation of another GJB2 allele do not increase the risk.

Deafness; GJB2 gene; p. V37I; Meta-analysis