Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 4 2025 12 24 221 225 Maryam Kamyab-Lari Department of Biology, School of Science, Shiraz University, Shiraz, Iran Mostafa Saadat Department of Biology, School of Science, Shiraz University, Shiraz, Iran 2025 11 12 2025 12 30 Background: Inflammation is involved in development of age-related macular degeneration (AMD), with the cGAS-STING pathway playing a critical role. This pathway activates in response to cytosolic DNA, such as accumulated mitochondrial DNA from aging or oxidative stress. Given STING's encoded by the STING1 gene, we hypothesized that functional STING1 polymorphisms might influence AMD susceptibility. Methods:  To identify the most relevant polymorphism, all polymorphisms of STING1 with MAF ≥1% were extracted from NCBI. The rs7380824 was selected for genotyping as it demonstrated the highest PSI value—a novel metric combining CADD score and MAF—indicating high potential deleteriousness. Then a hospital-based case-control study comprised 237 subjects (122 AMD patients, 115 controls) was carried out to investigate the association between the rs7380824 and the risk of AMD. Genotyping employed PCR-RFLP, and statistical analyses used logistic regression adjusted for age, smoking, and workplace exposure. Results: The genotypic frequency of the rs7380824 polymorphism was in Hardy-Weinberg equilibrium. No significant association was found between the genotypes of this polymorphism and AMD risk. However, a borderline protective effect was observed for the TT genotype versus CC+CT (OR=0.19, 95% CI: 0.03-1.16, p=0.073) after adjusting for age, workplace and smoking habits of the participants. Conclusion: As the first investigation of the association between the STING1 polymorphism (rs7380824) and AMD risk, this study did not identify a significant overall association. However, the observed protective effect of the TT genotype, potentially covered by the limited sample size, highlights the necessity for validation in studies with larger samples. https://abi.tums.ac.ir/index.php/abi/article/view/166 https://abi.tums.ac.ir/index.php/abi/article/download/166/128