含鈣尿路結石患者的MnSOD遺傳多態性調整由環境中三聚氰胺造成的氧化壓力和早期腎損傷之影響

黃詩婷^1,2、劉家駒^3-5、吳佳芳²、李永進^3,4,6、黃琮懿⁴、王巽玄⁶、詹鎮豪⁶、黃書彬^3,4、李經家^3,4、阮雍順^3,4、謝翠娟^1,2、蔡宜純⁷、陳主智^2,8、吳文正^3,4、吳明蒼^2,9,10

¹高雄醫學大學 醫學院 醫學研究所; ²高雄醫學大學 環境研究中心; ³高雄醫學大學 醫學院 泌尿學科; ⁴高雄醫學大學附設醫院 泌尿部; ⁵衛生福利部 屏東醫院 泌尿科; ⁶高雄市立小港醫院 泌尿科; ⁷高雄醫學大學附設醫院 內科部 腎臟科; ⁸國家衛生研究院 群體健康科學研究所; ⁹高雄醫學大學 醫學院 臨床醫學研究所; ¹⁰高雄醫學大學 健康科學院 公共健康學系

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

Shih-Ting Huang^1,2, Chia-Chu Liu^3-5, Chia-Fang Wu², Yung-Chin Lee^3,4,6, Tsung-Yi Huang⁴, Hsun-Shuan Wang⁶, Jhen-Hao Jhan⁶, Shu-Pin Huang^3,4, Ching-Chia Li^3,4, Yung-Shun Juan^3,4, Tusty-Jiuan Hsieh^1,2, Yi-Chun Tsai⁷, Chu-Chih Chen^2,8, Wen-Jeng Wu^3,4, Ming-Tsang Wu^2,9,10

¹Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University

²Research Center for Environmental Medicine, Kaohsiung Medical University

³Department of Urology, College of Medicine, Kaohsiung Medical University

⁴Department of Urology, Kaohsiung Medical University Hospital

⁵Depratment of Urology, Pingtung Hospital, Ministry of Health and Welfare

⁶Department of Urology, Kaohsiung Municipal Siaogang Hospital

⁷Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital

⁸Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes

⁹Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University

¹⁰Department of Public Health, College of Health Sciences, Kaohsiung Medical University

Purpose: Environmental melamine exposure increases the risk of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPX1), and catalase (CAT) can protect kidney against oxidative stress and maintain normal function. This study evaluated whether their single-nucleotide polymorphisms (SNPs) modified the effect of environmental melamine exposure on risk of oxidative stress and early kidney injury in adult patients with calcium urolithiasis.

Materials and Methods: Patients diagnosed with calcium urolithiasis were recruited from three hospitals in southwestern Taiwan between November, 2010 and January, 2015. All patients completed a structured questionnaire and provided one-spot overnight urine samples for the measurement of melamine levels, urinary biomarkers of oxidative stress, malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-OHdG), and renal tubular injury, N-Acetyl-β-D Glucosaminidase (NAG). Median values were used to dichotomize levels into high and low. Five SNPs (rs4880, rs5746136, rs1800668, rs1001179 and rs769217) were selected and identified using a TaqMan 5’ allelic discrimination assay.

Results: Three hundred and two patients (mean age of 54.5 ± 12.9 years) were enrolled. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high MDA 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 NAG levels than those carrying the A allele of rs5746136 and low melamine levels.

Conclusion: The SNPs of MnSOD, rs4880, and rs5746135, influence the risk of oxidative stress and renal tubular injury, respectively, in patients with calcium urolithiasis. In the context of high urinary melamine levels, their effect on oxidative stress and renal tubular injury risk was increased. There may be a need to take the SNPs of MnSOD into consideration when assessing the human tolerable daily intake of melamine especially in vulnerable populations.