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.
Highlights
Melamine is a synthetic chemical used in manufacturing a variety of commercial daily life products including housewares, countertops, fabrics, glues, and flame retardants [1,2].Because it has a high nitrogen content, it has been misused in animal feed and milk to deceptively elevate the protein content [1,2]
The current study found that two single-nucleotide polymorphisms (SNPs) of Manganese superoxide dismutase (MnSOD), rs4880 and rs5746136, modified the effects of melamine exposure on the risk of oxidative stress and renal tubular injury, respectively
This study found that two SNPs of MnSOD, rs4880 and rs5746136, modify the risks of oxidative stress and renal tubular injury, respectively
Summary
Melamine is a synthetic chemical used in manufacturing a variety of commercial daily life products including housewares, countertops, fabrics, glues, and flame retardants [1,2]. Because it has a high nitrogen content, it has been misused in animal feed and milk to deceptively elevate the protein content [1,2]. One probable mechanism that chronic low-dose melamine exposure could lead to early kidney injury and stone formation is its adverse effect on renal tubules, as was found by two of our human studies in melamine tableware workers [13] and adult patients with calcium urolithiasis [14]. We conducted an in vitro study by using human renal proximal tubular HK-2 cells and found that melamine could induce renal tubular damage by increasing oxidative stress [15]
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