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.