Association of UCP2 G (-866) A Polymorphism, but not NAT2 G (590) A, with Presbycusis Susceptibility in an Iranian Population

Background: Presbycusis, or age-related hearing loss, is a common sensory disorder in older adults. Oxidative stress is a major pathogenic mechanism, and polymorphisms in genes regulating detoxification and reactive oxygen species (ROS) balance, such as NAT2 and UCP2 , may influence disease susceptibility. Methods: We conducted a case–control study including 120 male presbycusis patients (mean age 65.1 years) and 120 age-matched healthy controls (mean age 63.4 years). Genotyping of the NAT2 590G>A (rs1799930) and UCP2 G (-866) A (rs659366) polymorphisms was performed using PCR-RFLP. Statistical analyses included odds ratios (ORs) with 95% confidence intervals (CIs), logistic regression, and Hardy–Weinberg equilibrium testing. Bioinformatics tools (including the UCSC Genome Browser, ORegAnno, and CpG island analysis) were used to predict the functional effects of variants. Results: No significant association was observed between NAT2 590G>A and presbycusis risk (OR = 1.22, 95% CI = 0.84–1.79, p = 0.289). In contrast, the UCP2 G(-866)A polymorphism showed a strong association: the AA genotype (OR = 3.20, 95% CI = 1.22–8.41, p = 0.018), A allele (OR = 1.68, 95% CI = 1.14–2.47, p = 0.008), and dominant GA+AA vs. GG model (OR = 1.84, 95% CI = 1.10–3.08, p = 0.02). Bioinformatics analysis indicated that the polymorphism may alter CpG islands in the promoter region and may could affect transcription factor binding and gene expression. Conclusion: Our findings suggest that the UCP2 G (-866) A polymorphism, but not NAT2 590G>A polymorphism, contributes to presbycusis susceptibility in the studied Iranian population. This variant could serve as a potential biomarker for the genetic risk assessment of presbycusis.