Systematic review and meta-analysis of pathogenic GJB2 variants in the Asian population

Define the extent to which pathogenic GJB2 (gap junction beta-2) variants are responsible for non-syndromic hearing loss (NSHL) in the Asian population.

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. CINAHL, Embase, and PubMed's MEDLINE were accessed from 1997 to 2023 using permutations of the MeSH terms: "Asian," ''Southeast Asian,'' "South Asian," "East Asian," "Southeastern Asian," and "GJB2." Additionally, all countries within the Indian subcontinent, Far East, and Southeast Asia, were included as key terms. Exclusion criteria included non-English publications, a non-Asian study population (per US Office of Management and Budget), and literature not investigating GJB2. An allele frequency analysis of pathogenic GJB2 variants in the Asian population was performed and stratified by country of origin.

One thousand one hundred and forty-one unique studies were identified, of which 420 met our inclusion criteria during the abstract screen. One hundred and ninety-five studies were included in the systematic review after full-text screen. Over 45 pathogenic variants were identified across 11 countries within the Indian subcontinent, Far East, and Southeast Asia. A total of 4,220,591 people from over 30 ethnic groups were included with ages ranging from 0 to 97 years. Of those with reported demographic information, 50 % (221,336/445,813) were female and 50 % (224,477/445,813) were male. The prevalence of pathogenic GJB2 variants varied by country, with common variants including c.235del; p.Leu79Cysfs∗3, c.109G > A; p.Val37Ile, and c.299_300del; p.His100Argfs∗14.

Variation in the prevalence of pathogenic GJB2 variants is likely due to the wide diversity of ancestral contributions in the Asian population. There are limited studies on the prevalence of GJB2 variants particularly for countries within the Indian subcontinent and Southeast Asia. Additional studies on the prevalence of GJB2 variants in these countries as well as ethnic sub-groups may be helpful in the development of assays for high throughput diagnosis for patients with hereditary hearing loss.