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ORIGINAL RESEARCH
Single nucleotide variant rs293795 OGG1 as a genetic risk factor for diabetic nephropathy
Kursk State Medical University, Kursk, Russia
Correspondence should be addressed: Iuliia E. Azarova
Yamskaya, 18, Kursk, 305041, Russia;Email: ur.xednay@razzzza
Funding: the study was supported by a grant from the Russian Science Foundation (project No. 25-25-20072) and the Ministry of Education and Science of the Kursk Region (agreement No. 241 dated May 19, 2025).
Author contribution: Semikina EV — genotyping of DNA samples, analysis of obtained data, writing of the text; Azarova YuE — concept and design of the study, fundraising, collection and processing of materials, writing of the text; Panichev SA — genotyping of DNA samples, entering genotyping results into the database; Basareva OI — selection of functionally significant polymorphic variants of the OGG1 gene, selection of primers and probes for SNP genotyping; Dzhanchatova NV — genotyping of DNA samples; Alferova EYu — sample preparation: DNA extraction from blood, measurement of concentration and purity of DNA samples; Polonikov AV — analyzed the data, reviewed the literature, and made final edits. The authors approved the version for publication and agreed to be accountable for all aspects of the work, ensuring that any questions related to the accuracy and integrity of any part of it are properly reviewed and resolved.
Compliance with ethical standards: the study was approved by the Regional Ethics Committee at Kursk State Medical University (meeting minutes No. 1 dated January 20, 2025).
Diabetic nephropathy (DNP) is a serious complication of type 2 diabetes mellitus (T2D), leading to early disability and mortality from end-stage renal failure. Experimental and clinical studies have shown the leading role of oxidative stress-induced damage to macromolecules, including DNA, in the development and progression of DNF against the background of hyperglycemia. On the contrary, repair of these DNA lesions serves as a signal to end ongoing oxidative stress. The key DNA repair enzyme is 8-oxoguanine DNA glycosylase, encoded by the OGG1 gene. The aim of this study was to analyze the associations of five polymorphic variants (rs2072668, rs1052133, rs293795, rs2304277, and rs6443265) of the OGG1 gene with the risk of developing DNF in patients with type 2 diabetes. The study included 1461 patients with type 2 diabetes, 577 of whom were diagnosed with DNF. DNA genotyping was performed by real-time polymerase chain reaction using allele-specific fluorescently labeled probes. Associations were established between the rs293795-G/G genotype (OR = 1.97, 95% CI = 1.23-3.16, p = 0.007) and the rs2072668C-rs1052133C-rs293795G-rs2304277G-rs6443265C haplotype (OR = 1.30, 95% CI = 1.06-1.60, p = 0.012) of the OGG1 gene with a predisposition to DNF in the background of T2D. Moreover, six OGG1 diplotypes associated with an increased risk of DNF and one diplotype associated with a reduced risk of DNF in patients with T2D were identified. Thus, in our study, we presented for the first time data on the association of the OGG1 gene polymorphism with DNF, which creates a scientific foundation for further research on the contribution of disturbances in the DNA oxidative damage repair system to the development of microvascular complications of T2D.
Keywords: type 2 diabetes mellitus, real-time PCR, genetic predisposition, diabetic nephropathy, DNA glycosylases, DNA repair, OGG1, genotyping methods