Interplay between Superoxide Dismutase, Glutathione Peroxidase, and Peroxisome Proliferator Activated Receptor Gamma Polymorphisms on the Risk of End‐Stage Renal Disease among Han Chinese Patients

Abstract

Background. Single nucleotide polymorphisms (SNPs) of antioxidants, including superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), play an important role in the risk for cancer and metabolic disorders. However, little is known regarding the effect of antioxidant SNPs on renal events. Methods. We prospectively enrolled multicenter patients with end-stage renal disease (ESRD) and those without chronic kidney disease (CKD) of Han Chinese origin, with SOD2 (Val16Ala), GPX1 (Pro197Leu), and PPAR-γ (Pro12Ala, C161T) genotyped. Multiple regression analyses were conducted to evaluate the significant risk determinants for ESRD. Results. Compared to ESRD patients, non-CKD subjects were more likely to have T allele at SOD2 Val16Ala (p = 0.036) and CC genotype at PPAR-γ Pro12Ala (p = 0.028). Regression analysis showed that TT genotype of SOD2 Val16Ala conferred significantly lower ESRD risk among patients without diabetes (odds ratio 0.699; p = 0.018). GPX1 SNP alone did not alter the risk. We detected significant interactions between SNPs including PPAR-γ Pro12Ala, C161T, and GPX1 regarding the risk of ESRD. Conclusion. This is the first and largest study on the association between adverse renal outcomes and antioxidant SNPs among Han Chinese population. Determination of SOD2 and PPAR-γ SNPs status might assist in ESRD risk estimation.

Heavy alcohol drinking downregulates ALDH2 gene expression but heavy smoking up-regulates SOD2 gene expression in head and neck squamous cell carcinoma

“…Heavy alcohol drinking can cause liver damage and activate intrinsic prothrombin activation pathway, especially in the ALDH2 lowexpression group. Chao et al have reported the interplay between superoxide dismutase genes and PPAR signaling [26]. In our study, the SOD2 high-expression group showed decreased PPAR signaling pathway (Table 2).…”

Polymorphism Pro12→Ala of the peroxisome proliferator-activated receptors gamma gene effect on lipid peroxidation and antioxidant defense in patients with type 2 diabetes

“…Today, the influence of polymorphisms rs1801282 of gene PPARG on oxidative processes and antioxidant is not in doubt. A recent study conducted by Chia-Ter Chao (2016) demonstrated Pro 12 →Ala association with increasing SOD activity in renal disease (P<0.028) [9]. We also found the intensification of LPO in carriers of alleles 12Pro in polymorphism Pro 12 →Ala of gene PPARG, whereas a significant decrease in activity of the enzyme catalase links AOC in patients with type 2 diabetes, was found as in the case of polymorphism Pro 12 →Pro of gene PPARG, and as in the presence of the allele 12Pro in this genotype [10].…”

“…In the pathogenesis of type 2 diabetes is activated by excessive formation of reactive oxygen species, leading to an intensification of LPO and oxidative stress, which takes a leading role in the development of complications [8][9][10]. Proved, that type 2 diabetes -a free radical pathology [3].…”

Diabetes mellitus, superoxide dismutase and peroxisome proliferator activated receptor gamma polymorphisms modify the outcome of end‐stage renal disease patients of Han Chinese origin

“…Certain SNP of the GPX1 gene is also found to increase the risk of renal events among patients with type 1 DM, and correlates with higher plasma ROS markers . Previously, we also discovered that TT genotype of exon 2 of the SOD2 gene (rs4880) conferred a significantly lower risk of presenting ESRD among patients without DM ( P = 0.014) . On the other hand, very few studies address the effect of antioxidant SNPs on the survival of ESRD patients.…”