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.