Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients

Abstract

Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine’s effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-β-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased.

Molecular docking analysis of melamine with nuclear factor erythroid 2-related factor 2 and succinate dehydrogenase

“…Guo et al showed that melamine activates the NF-κB/cox-2 and NOX/ROS pathways that induce inflammation and oxidative stress highlighting the significant role of NOX in melamine-induced ROS formation [ 5 ]. A recent study showed the effect of single-nucleotide polymorphisms (SNPs) in Manganese superoxide dismutase (MnSOD) enzyme which could modify the protective response of antioxidant enzyme toward melamine induced oxidative stress and increases the risk of renal tubular injury in calcium urolithiasis patients [ 6 ]. Another study investigated the effects of melamine containing diets on the various parameters of Oreochromisniloticus and showed that melamine significantly reduced the activity of superoxide dismutase and glutathione peroxidase [ 7 ].…”