Association of a common SOD gene variant with ARHL risk: analysis by age, hearing threshold, and enzyme activity.

AIM This study aimed to investigate the association between the superoxide dismutase 2 (SOD2)-rs4880 polymorphism and age-related hearing loss (ARHL) in an Iranian population, assessing its impact on age, hearing loss severity, and SOD activity, alongside bioinformatics and molecular docking analyses with TOM20. MATERIALS AND METHODS This case-control study included 145 ARHL patients and 155 healthy controls. Serum SOD activity was measured using a commercial kit and rs4880 genotyping was done via PCR-RFLP. Bioinformatics tools focusing on HADDOCK-2.4 were used to assess the interaction between SOD2 signal peptides and the TOM20 receptor. RESULTS The TT genotype and T allele were associated with increased ARHL risk (OR =1.98, p = 0.032; OR = 1.48, p = 0.018), with a stronger effect in individuals older than 60 years. Serum SOD activity was significantly lower in patients (12.05 ± 2.04 U/ml) than controls (12.62 ± 2.04 U/ml, p = 0.017). Bioinformatics data revealed that the mutant variant exhibits 34% lower alpha-helix propensity compared to the wild-type. Docking results confirmed a weaker binding affinity for the mutant variant compared to the wild-type, suggesting inefficient recognition and recruitment by the mitochondrial import machinery. CONCLUSION The SOD2-rs4880 polymorphism may disrupt mitochondrial import via TOM20 and can be considered a molecular risk factor for ARHL, especially in older age.