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The angiotensin-I converting enzyme gene I/D variation contributes to end-stage renal disease risk in Chinese patients with type 2 diabetes receiving hemodialysis

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Abstract

Whether the DD genotype of the angiotensin-I converting enzyme (ACE) I/D variation contributes to end-stage renal disease (ESRD) risk in type 2 diabetes mellitus (T2DM) remains controversial. Differences in study design, case and control definition, sample size and ethnicity may contribute to the discrepancies reported in association studies. We performed a case–control study to evaluate the association of the ACE I/D variation with ESRD risk in Chinese patients with T2DM receiving hemodialysis and analyzed the genotype–phenotype interaction. Unrelated Chinese patients (n = 432) were classified into the non-diabetic nephropathy (DN) control group (n = 222, duration of diabetes >10 years, no signs of renal involvement) and the DN-ESRD group (n = 210; ESRD due to T2DM, receiving hemodialysis). Polymerase chain reaction was used to genotype ACE I/D for all 432 subjects. The frequencies of the ID + DD genotypes were higher in the DN-ESRD group than non-DN control group (65.2 vs. 50.9 %; adjusted OR 1.98 (95 % CI, 1.31–3.00; P = 0.001). In the DN-ESRD group, the DD genotypic subgroup had significantly elevated HbA1c and diastolic blood pressure (DBP) compared to the II subgroup (both P < 0.05). The DD genotype of the ACE I/D variation may be associated with more elevated blood pressure and HbA1c, and therefore may predict the development, progression and severity of DN-ESRD in Chinese patients with T2DM undergoing hemodialysis.

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Acknowledgments

This work was supported by grants from the Project of National Natural Science Foundation of China (81471012, 81270876, 30771022, and 30971384), the University Innovation Research and Training Program of Shanghai Jiaotong University School of Medicine (2015301), the Shanghai Leading Talent (SLJ15055), the Program of Education Research from Shanghai Jiaotong University of Medicine (YB150612), and Program of Scientific Research from Shanghai Health and Family Planning Commission (20144Y0206). Y. Liu was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grant SC1DK104821.

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    Authors and Affiliations

    1. Department of Endocrinology & Metabolism, Putuo Hospital Attached to Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200000, China

      Ming Lu, Ming Yu & Tao Lei

    2. Department of Endocrinology, China-Japan Union Hospital of Jilin University, 829 Xinmin Street, Changchun, China

      Jianzhong Zhang

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

      Ming Li, Xiaoxu Ge, Can Li, Rong Zhang, Weijing Zhao, Taishan Zheng, Yuqian Bao, Limei Liu & Weiping Jia

    4. Shanghai Jiaotong University School of Medicine, 227 Chongqing South Road, Shanghai, 200025, China

      Xu Dai, Jiao Zhao, Mingzhou Fu, Tao Wang & Xiyao Fang

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

      Feng Wang & Niansong Wang

    6. 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. Ming Lu
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    Correspondence to Limei Liu.

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    Ming Lu, Jianzhong Zhang and Ming Li contributed equally to this work.

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    Lu, M., Zhang, J., Li, M. et al. The angiotensin-I converting enzyme gene I/D variation contributes to end-stage renal disease risk in Chinese patients with type 2 diabetes receiving hemodialysis. Mol Cell Biochem 422, 181–188 (2016). https://doi.org/10.1007/s11010-016-2819-6

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