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Arg913Gln of SLC12A3 gene promotes development and progression of end-stage renal disease in Chinese type 2 diabetes mellitus

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Abstract

Whether the Arg913Gln variation (rs11643718, G/A) of SLC12A3 contributes to diabetic nephropathy (DN) remains controversial. We undertook a case–control study to evaluate the association of the SLC12A3-Arg913Gln variation with the risk of end-stage renal disease (ESRD) in Chinese type 2 diabetes mellitus (T2DM) patients undergoing hemodialysis, and analyzed the genotype–phenotype interaction. Unrelated Chinese T2DM patients (n = 372) with diabetic retinopathy were classified into the non-DN (control) group (n = 151; duration of T2DM >15 years, no signs of renal involvement) and the DN–ESRD group (n = 221; ESRD due to T2DM, receiving hemodialysis). Polymerase chain reaction-direct sequencing was used to genotype the SLC12A3-Arg913Gln variation for all participants. The frequency of the GA+AA genotype in the DN–ESRD group was significantly higher than that of the non-DN group (23.1 vs. 9.9%; adjusted OR 2.2 (95% CI 1.3–4.5), P = 0.019). In the non-DN group, GA+AA carriers had a significantly higher urinary albumin excretion rate (UAER) and diastolic blood pressure compared with GG carriers (both P < 0.05). The SLC12A3-Arg913Gln variation may be associated with increased blood pressure and UAER and, therefore, could be used to predict the development and progression of DN–ESRD in Chinese T2DM patients undergoing hemodialysis.

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Acknowledgements

This work was supported by grants from the Project of National Natural Science Foundation of China (81471012, 81270876, 30771022 and 30971384), the Shanghai Leading Talent (SLJ15055), and the Program of Education Research from Shanghai Jiaotong University of Medicine (YB150612). Y. Liu was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant SC1DK104821.

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Author notes

  1. Rong Zhang, Langen Zhuang, and Ming Li have contributed equally to this work.

Authors and Affiliations

  1. Shanghai Key Laboratory of Diabetes, Department of Endocrinology & Metabolism, Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, China

    Rong Zhang, Ming Li, Juan zhang, Wei**g Zhao, ** Jia

  2. Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China

    Langen Zhuang

  3. Department of Nephrology, Shanghai Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, China

    Feng Wang & Niansong Wang

  4. Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Sciences, University of California Los Angeles (UCLA) School of Medicine, Los Angeles, CA, USA

    Yanjun Liu

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  1. Rong Zhang
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Correspondence to Limei Liu.

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Zhang, R., Zhuang, L., Li, M. et al. Arg913Gln of SLC12A3 gene promotes development and progression of end-stage renal disease in Chinese type 2 diabetes mellitus. Mol Cell Biochem 437, 203–210 (2018). https://doi.org/10.1007/s11010-017-3120-z

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