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Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis

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Abstract

Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12–1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08–1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P < 0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (81230027, 81401127, 81471219), Shanghai Natural Science Foundation (13ZR1460500, 13ZR1409700), Shanghai Excellent Academic Leaders Project (14XD1403400), Shanghai Key Laboratory of Psychotic Disorders (13dz2260500-14-K06), Shanghai Changhai Hospital Foundation (CH125530900), and Postdoctoral Grant of Secondary Military Medical University. We would like to acknowledge the reviewers for their helpful comments on this paper.

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Authors and Affiliations

  1. Department of Neurology, Shanghai Changhai Hospital, Secondary Military Medical University, No. 168 Changhai Road, Shanghai, 200433, China

    Shuai Wu, Yan Han & Yangtai Guan

  2. Department of Psychology, Qiqihar Mental Health Center, Qiqihar, 161000, China

    Qiang Hu

  3. Department of Pathology, Qiqihar Medical University, Qiqihar, 161000, China

    **aojie Zhang

  4. Mental Health Institute, Qiqihar Medical University, Qiqihar, 161000, China

    Guangcheng Cui

  5. Department of Neurology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Zezhi Li

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  1. Shuai Wu
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Correspondence to Zezhi Li or Yangtai Guan.

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Wu, S., Han, Y., Hu, Q. et al. Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis. Mol Neurobiol 54, 2435–2444 (2017). https://doi.org/10.1007/s12035-016-9823-4

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