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Heterogeneous impact of type 2 diabetes mellitus-related genetic variants on gestational glycemic traits: review and future research needs

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Abstract

Gestational glucose homeostasis influences mother’s metabolic health, pregnancy outcomes, fetal development and offspring growth. To understand the genetic roles in pregnant glucose metabolism and genetic predisposition for gestational diabetes (GDM), we reviewed the recent literature up to Jan, 2018 and evaluated the influence of T2DM-related genetic variants on gestational glycemic traits and glucose tolerance. A total of 140 variants of 89 genes were integrated. Their associations with glycemic traits in and outside pregnancy were compared. The genetic circumstances underlying glucose metabolism exhibit a similarity between pregnant and non-pregnant populations. While, not all of the T2DM-associated genetic variants are related to pregnant glucose tolerance, such as genes involved in fasting insulin/C-peptide regulation. Some genetic variants may have distinct effects on gestational glucose homeostasis. And certain genes may be particularly involved in this process via specific mechanisms, such as HKDC1, MTNR1B, BACE2, genes encoding cell cycle regulators, adipocyte regulators, inflammatory factors and hepatic factors related to gestational glucose sensing and insulin signaling. However, it is currently difficult to evaluate these associations with quantitative synthesis due to inadequate data, different analytical methods, varied measurements for glycemic traits, controversies in diagnosis of GDM, and unknown ethnicity- and/or sex-related influences on pregnant maternal metabolism. In conclusion, different genetic associations with glycemic traits may exist between pregnant and non-pregnant conditions. Comprehensive research on specific genetic regulation in gestation is necessary.

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Acknowledgements

Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from website of http://www.magicinvestigators.org. Also, data on T2DM have been downloaded by DIAGRAM consortium.

Funding

This study was funded by the National Natural Science Foundation of China (81471430).

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  1. Shasha Liu and Yunqiang Liu: co-first authors.

Authors and Affiliations

  1. Diabetes Center and Transplantation Translational Medicine, Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Yihuanlu **erduan 32#, Chengdu, 610072, China

    Shasha Liu & Shunyao Liao

  2. Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China

    Yunqiang Liu

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  1. Shasha Liu
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Correspondence to Shunyao Liao.

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Shasha Liu declares that she has no conflict of interest. Yunqiang Liu declares that he has no conflict of interest. Shunyao Liao declares that she has no conflict of interest.

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Liu, S., Liu, Y. & Liao, S. Heterogeneous impact of type 2 diabetes mellitus-related genetic variants on gestational glycemic traits: review and future research needs. Mol Genet Genomics 294, 811–847 (2019). https://doi.org/10.1007/s00438-019-01552-0

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