SNTB1 gene polymorphisms and risk of high myopia: meta-analysis and single-center validation

Purpose Genetic polymorphisms in syntrophin beta-1 (SNTB1) have been implicated in altering protein function or expression, potentially influencing ocular growth regulation. Genome-wide association studies (GWASs) suggest that specific SNTB1 variants may correlate with high myopia susceptibility across diverse populations. However, findings remain inconsistent, highlighting the need for further investigation into population-specific genetic effects and underlying mechanisms. Methods Accordingly, the PubMed and Wanfang databases were searched for articles published until June 1, 2025, using the keywords SNTB1 or syntrophin beta-1, polymorphism, and myopia or shortsightedness. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to examine the association. The SNTB1 rs6469937 polymorphism genotypes were identified with the TaqMan assay. Results Four related studies were conducted to better understand the association between SNTB1 gene polymorphisms and high myopia risk. The SNTB1 rs4455882 site was associated with a decreased overall high myopia risk (e.g., G vs. A; OR = 0.815; 95% CI, 0.688–0.984; pheterogeneity = 0.465; p = 0.017). Similar trends were detected in the rs4395927 site (e.g., T vs. C; OR = 0.791; 95% CI, 0.670–0.935; pheterogeneity = 0.199; p = 0.006) and rs6469937 site (e.g., A vs. G; OR = 0.811; 95% CI, 0.697–0.944; pheterogeneity = 0.030; p = 0.007). Furthermore, high myopia patients carrying the SNTB1 rs6469937 AA+AG genotypes exhibited pronounced increases in serum levels of SNTB1 compared to the GG genotype (p < 0.01) but showed an opposite trend compared to genotype-matched normal controls (p < 0.05). Conclusions The current study suggested that the SNTB1 rs4455882, rs4395927, and rs6469937 polymorphisms may be potential influencing factors of high myopia. Furthermore, the rs6469937 polymorphism may offer value as a candidate variant requiring validation that can aid in the early identification and prognostic evaluation of high myopia.