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The roles of endothelial nitric oxide synthase gene polymorphisms in diabetes mellitus and its associated vascular complications: a systematic review and meta-analysis

Endocrine volume 62, pages 412–422 (2018)Cite this article

Abstract

Purpose

The roles of endothelial nitric oxide synthase (eNOS) gene polymorphisms in diabetes mellitus (DM) were intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between eNOS genetic variations and DM.

Methods

Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess correlations between eNOS polymorphisms and DM.

Results

A total of 91 studies were finally included in our analyses. Significant associations with the susceptibility to DM were detected for the rs891512, rs1799983, rs2070744, and rs869109213 polymorphisms. As for vascular complications in DM, significant associations with the susceptibility to diabetic nephropathy were detected for the rs1799983 and rs2070744 polymorphisms. In addition, we also found that the rs1799983 polymorphism was significantly associated with the susceptibility to peripheral artery disease, whereas the rs2070744 polymorphism was significantly associated with the susceptibility to coronary artery disease in DM patients. Further subgroup analyses on the basis of type of disease and ethnicity of participants showed similar positive results.

Conclusions

In conclusion, our findings indicate that rs891512, rs1799983, rs2070744, and rs869109213 polymorphisms may serve as genetic biomarkers of DM, while rs1799983, rs2070744, and rs869109213 polymorphisms may contribute to the development of vascular complications in DM.

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Authors contributions

J.D. and Y.Z. conceived of the study, participated in its design. J.D. and P.Y. conducted the systematic literature review. J.D., P.Y., and Y.W. performed data analyses. J.D. and Y.Z. drafted the manuscript. All authors have read and approved the final manuscript.

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Author notes

    Affiliations

    1. Department of Clinical Nutrition, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, Shandong, China

      Jinnan Dong

    2. Department of Clinical Nutrition, Yantaishan Hospital, Yantai, 264001, Shandong, China

      Yu Ping

    3. Hemodialysis Room, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, Shandong, China

      Yuhong Wang

    4. Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, 261031, Shandong, China

      Yang Zhang

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    1. Jinnan Dong
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    2. Yu Ping
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    4. Yang Zhang
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    Correspondence to Yang Zhang.

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    The authors declare that they have no conflict of interest.

    Additional information

    These authors contributed equally: Jinnan Dong, Ping Yu.

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    Dong, J., Ping, Y., Wang, Y. et al. The roles of endothelial nitric oxide synthase gene polymorphisms in diabetes mellitus and its associated vascular complications: a systematic review and meta-analysis. Endocrine 62, 412–422 (2018). https://doi.org/10.1007/s12020-018-1683-4

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    • DOI: https://doi.org/10.1007/s12020-018-1683-4

    Keywords

    • Endothelial nitric oxide synthase (eNOS)
    • Gene polymorphisms
    • Diabetes mellitus (DM)
    • Systematic review
    • Meta-analysis