Impact of a 50bp insertion/deletion polymorphism of the superoxide dismutase-1 on oxidative stress status and risk of keratoconus

Keratoconus (KC) is characterized by the predominant primary ectatic disease, affecting the cornea, necessitating corneal transplants in some cases. While some loci associated with KC risk have been identified, the understanding of the disease remains limited. Superoxide dismutase (SOD) enzymes play a crucial role in countering the reactive oxygen species and providing protection against oxidative stress (OS). Accordingly, the objective of this study was to investigate a potential association of a 50 nucleotide base pairs (bp) insertion/deletion (I/D) within the SOD1 promoter, and the located 1684 bp upstream of the SOD1 ATG, with KC in the Iranian population. Additionally, an assessment was conducted on SOD activity and the total antioxidant capacity (TAC), as determined by the ferric reducing-antioxidant power assay, along with malondialdehyde (MDA) levels. In this case-control study, genomic DNA was extracted from the blood cells of KC (n = 402) and healthy (n = 331) individuals. The genotype of this gene was determined using the PCR technique. Furthermore, the amount of SOD enzyme activity and the MDA and TAC levels were measured in the serum of the study groups. The (I/I) genotype was present in 84.23%, the (I/D) genotype in 15.06%, and the (D/D) genotype in 0.69% of both groups. A statistically significant relationship was seen between different genotypes and TAC, MDA, and SOD1 activity indices (P < 0.05). Individuals with the D/D genotype exhibited a decrease in total antioxidant capacity, an increase in the amount of MDA, and a decrease in SOD1 enzyme activity (P < 0.05). Moreover, the logistic regression analysis of KC development indicated that elevated levels of MDA increased the risk of KC incidence in the patient group compared to the healthy group, while a higher activity of SOD1 and greater values of TAC decreased the KC risk. The removal of the 50 bp fragment reduced SOD1 activity and elevated OS levels, thereby impacting the oxidant-antioxidant balance. This could potentially play a significant role in individuals afflicted by KC.