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Oxidative stress has been hypothesized to play a crucial role in the complications of type 2 diabetes (T2D). Hyperglycaemia-mediated increases in free radicals have a deleterious effect on cellular compartments and nucleic acids, leading to imbalances between free radicals and antioxidant enzymes. This case–control study comprised two groups with 100 participants (50 T2D and 50 DN patients) and aimed to examine the association between single-nucleotide polymorphisms (SNPs) in the genes encoding nicotinamide adenine dinucleotide phosphate oxidase (NOX), glutathione S-transferase P (GSTP1), and glutathione peroxidase 1(GPX1) and diabetic nephropathy (DN) risk in patients with T2D. An SNP genotyping assay was performed using TaqMan assay and real-time PCR to identify the SNPs (NOXrs4673, GSTPrs1695, GPX1rs1050450). The Sanger method was used to validate our findings. Fisher chi-square analyses revealed no significant differences in these genes when comparing T2D patients with and without DN. Our findings suggest no association between the rs4673, rs1695, and rs1050450 SNPs and DN in Saudi patients with T2D.

One of the complications of diabetes mellitus (DM) is diabetic nephropathy (DN), which plays a significant role in the progression of end‐stage renal disease. Oxidative stress is implicated in DN pathogenesis, and genetic variations in antioxidant enzymes such as superoxide dismutase 2 (SOD2) and catalase (CAT) may contribute to the susceptibility. This study aimed to investigate the potential association between single nucleotide polymorphisms (SNPs) in antioxidant enzymes, specifically SOD2rs4880 and CAT rs769217, and the risk of T2D and susceptibility to DN within the Saudi population. This case–control study included 150 participants, comprising 50 patients with T2D without DN (group 1), 50 patients with T2D with DN (group 2), and 50 healthy participants (group 3). The samples were genotyped using real‐time PCR for SOD2rs4880 and CATrs769217 SNPs. Sanger sequencing was used for validation. Statistical analyses were performed to explore associations between these SNPs and T2D with or without DN. No significant difference was observed in CATrs769217 expression between the groups. However, a significant difference was observed in SOD2rs4880 expression between the healthy controls and patients with T2D with DN (p= .028). Furthermore, SOD2rs4880 was associated with approximately threefold increased risk of DN in patients with T2D compared to that in healthy participants (odds ratio [OR] = 2.99 [1.31–6.83]). Validation through Sanger sequencing further confirmed these findings. The findings of this study provide evidence that SOD2rs4880 SNP may contribute to inadequate defence by the antioxidant enzyme, SOD2, against DM‐induced oxidative stress and thus cause DN in Saudi patients with T2D. Therefore, SOD2rs4880 may serve as a predictive marker to prevent the development and progression of DN in patients with T2D. Our findings revealed a statistically significant difference between the healthy control group and T2D patients with DN regarding the expression of SOD2 SNP. No significant difference was observed in the expression of CAT SNP between the groups. These data provide evidence that the SOD2 SNP might contribute to improper defence of the SOD2 enzyme against diabetes‐induced oxidative stress and cause the DN in Saudi patients with T2D.