The association of RAGE gene polymorphisms with inflammatory and oxidative stress markers in diabetic kidney disease patients.

Introduction: The receptor for advanced glycation end products (RAGE) plays a significant role in diabetic kidney disease (DKD) complications.

Materials and methods: This study examined the association between RAGE gene polymorphisms (rs2070600 and rs184003) and inflammatory and oxidative stress markers in DKD. Fifty DKD patients and fifty healthy controls were enrolled.

Results: For the rs2070600 variant, the CC genotype and C allele frequencies were 64% and 82% in DKD patients, respectively, while the TT genotype was more prevalent in controls (P = 0.002). The A allele homozygous genotype of rs184003 was more common in controls than in DKD patients (P = 0.037). Furthermore, haplotype association and linkage disequilibrium (LD) analyses were performed, and the findings revealed that the C-C and A-T haplotypes were significantly more frequent in DKD patients and healthy controls, respectively. In DKD patients, a significant increase in myeloperoxidase (MPO) and catalase (CAT) activities and a decrease in glutathione peroxidase (GPx) activity were observed (P < 0.001). Serum concentrations of IL-6 (13.63 ± 5.89 pg/mL vs. 4.93 ± 1.74 pg/mL; P < 0.001) and TNF-α (58.19 ± 26.48 pg/mL vs. 12.69 ± 5.71 pg/mL; P < 0.001) were significantly elevated in the DKD group. For rs184003, the A allele and AA genotype were more common in controls, suggesting a reduced DKD risk. In individuals with the CC and CT genotypes for rs2070600 and the CC, CA, and AA genotypes for rs184003, elevated malondialdehyde, IL-6, TNF-α, and MPO activity were observed, alongside reduced CAT and GPx activities.

Conclusion: RAGE polymorphisms may contribute to increased oxidative stress and reduced antioxidant capacity in DKD, underscoring their role in the disease's pathogenesis.