Genetic variation of rs3811463 is associated with gestational diabetes mellitus susceptibility

Liu,Yun; Ge,Zhi‑Ping; Sun,Li‑Zhou; Tong,Pei; Lu,Hong‑Mei

doi:10.3892/etm.2017.5188

Genetic variation of rs3811463 is associated with gestational diabetes mellitus susceptibility

Authors:
- Yun Liu
- Zhi‑Ping Ge
- Li‑Zhou Sun
- Pei Tong
- Hong‑Mei Lu
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Affiliations: Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Obstetrics, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Women and Children Health Hospital, Nanjing, Jiangsu 210029, P.R. China
Published online on: September 22, 2017 https://doi.org/10.3892/etm.2017.5188
Pages: 5157-5162

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Abstract

Gestational diabetes mellitus (GDM) is a growing health concern, and it increases the risk of adverse pregnancy outcomes with substantial long‑term adverse health impacts on mothers and their offspring. Several studies have revealed specific associations between genetic variants and the risk of GDM. Single nucleotide polymorphisms (SNPs) are the major type of genetic variation in humans. Let‑7 microRNA targets are enriched for genes containing SNPs associated with glucose metabolism, including Lin28. In the present study, the effect of T/C variants of rs3811463 (a SNP located near to the let‑7 binding site in Lin28) on GDM risk was investigated. A GDM rat model was successfully constructed using a high fat diet and streptozotocin injection, and the primary skeletal muscle cells were isolated. The cell transfection results demonstrated that rs3811463‑T/C significantly affected the glucose uptake and insulin sensitivity. Reverse transcription‑quantitative polymerase chain reaction analysis indicated that the C allele at rs3811463 regulated the expression of glucose metabolism‑associated genes insulin‑like growth factor two binding protein 2 and glucokinase. Western blot analysis data revealed that replacement of the T allele by the C allele at rs3811463 modulated the protein level of Sirtuin 1. Taken together, it was concluded that the let‑7/Lin28 axis regulated glucose uptake and insulin sensitivity by modulating the expression of glucose metabolism‑associated proteins. These findings provide novel evidence on the association between genetic variations of rs3811463 and GDM susceptibility.

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1	Russo LM, Nobles C, Ertel KA, Chasan-Taber L and Whitcomb BW: Physical activity interventions in pregnancy and risk of gestational diabetes mellitus: A systematic review and meta-analysis. Obstet Gynecol. 125:576–582. 2015. View Article : Google Scholar : PubMed/NCBI
2	Zhang C and Ning Y: Effect of dietary and lifestyle factors on the risk of gestational diabetes: Review of epidemiologic evidence. Am J Clin Nutr. 94 6 Suppl:1975S–1979S. 2011. View Article : Google Scholar : PubMed/NCBI
3	Bowers K, Tobias DK, Yeung E, Hu FB and Zhang C: A prospective study of prepregnancy dietary fat intake and risk of gestational diabetes. Am J Clin Nutr. 95:446–453. 2012. View Article : Google Scholar : PubMed/NCBI
4	Donin AS, Nightingale CM, Owen CG, Rudnicka AR, Jebb SA, Ambrosini GL, Stephen AM, Cook DG and Whincup PH: Dietary energy intake is associated with type 2 diabetes risk markers in children. Diabetes Care. 37:116–123. 2014. View Article : Google Scholar : PubMed/NCBI
5	Nicoloso MS, Sun H, Spizzo R, Kim H, Wickramasinghe P, Shimizu M, Wojcik SE, Ferdin J, Kunej T, Xiao L, et al: Single-nucleotide polymorphisms inside microRNA target sites influence tumor susceptibility. Cancer Res. 70:2789–2798. 2010. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
7	Shukla GC, Singh J and Barik S: MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 3:83–92. 2011.PubMed/NCBI
8	Nguyen LH and Zhu H: Lin28 and let-7 in cell metabolism and cancer. Transl Pediatr. 4:4–11. 2015.PubMed/NCBI
9	Sun X, Liu J, Xu C, Tang SC and Ren H: The insights of Let-7 miRNAs in oncogenesis and stem cell potency. J Cell Mol Med. 20:1779–1788. 2016. View Article : Google Scholar : PubMed/NCBI
10	Viswanathan SR, Daley GQ and Gregory RI: Selective blockade of microRNA processing by Lin28. Science. 320:97–100. 2008. View Article : Google Scholar : PubMed/NCBI
11	Zhu H, Shyh-Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, et al: The Lin28/let-7 axis regulates glucose metabolism. Cell. 147:81–94. 2011. View Article : Google Scholar : PubMed/NCBI
12	Chen AX, Yu KD, Fan L, Li JY, Yang C, Huang AJ and Shao ZM: Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility. PLoS Genet. 7:e10022592011. View Article : Google Scholar : PubMed/NCBI
13	Zhang J, Zhang L, Fan R, Guo N, Xiong C, Wang L, Jin S, Li W and Lu J: The polymorphism in the let-7 targeted region of the Lin28 gene is associated with increased risk of type 2 diabetes mellitus. Mol Cell Endocrinol. 375:53–57. 2013. View Article : Google Scholar : PubMed/NCBI
14	Johnson AM and Olefsky JM: The origins and drivers of insulin resistance. Cell. 152:673–684. 2013. View Article : Google Scholar : PubMed/NCBI
15	Veerapur VP, Prabhakar KR, Kandadi MR, Srinivasan KK and Unnikrishnan MK: Antidiabetic effect of Dodonaea viscosa aerial parts in high fat diet and low dose streptozotocin-induced type 2 diabetic rats: A mechanistic approach. Pharm Biol. 48:1137–1148. 2010. View Article : Google Scholar : PubMed/NCBI
16	Chang HC and Guarente L: SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 25:138–145. 2014. View Article : Google Scholar : PubMed/NCBI
17	El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, El-Sayed M and Takewaki T: Successful abrogation by thymoquinone against induction of diabetes mellitus with streptozotocin via nitric oxide inhibitory mechanism. Int Immunopharmacol. 5:195–207. 2005. View Article : Google Scholar : PubMed/NCBI
18	Mondol V and Pasquinelli AE: Let's make it happen: The role of let-7 microRNA in development. Curr Top Dev Biol. 99:1–30. 2012. View Article : Google Scholar : PubMed/NCBI
19	Thornton JE and Gregory RI: How does lin28 let-7 control development and disease? Trends Cell Biol. 22:474–482. 2012. View Article : Google Scholar : PubMed/NCBI
20	Frost RJ and Olson EN: Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. Proc Natl Acad Sci USA. 108:pp. 21075–21080. 2011; View Article : Google Scholar : PubMed/NCBI
21	Zhang C, Bao W, Rong Y, Yang H, Bowers K, Yeung E and Kiely M: Genetic variants and the risk of gestational diabetes mellitus: A systematic review. Hum Reprod Update. 19:376–390. 2013. View Article : Google Scholar : PubMed/NCBI
22	Petrie JR, Pearson ER and Sutherland C: Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology. Biochem Pharmacol. 81:471–477. 2011. View Article : Google Scholar : PubMed/NCBI
23	Rutanen J, Yaluri N, Modi S, Pihlajamäki J, Vänttinen M, Itkonen P, Kainulainen S, Yamamoto H, Lagouge M, Sinclair DA, et al: SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity. Diabetes. 59:829–835. 2010. View Article : Google Scholar : PubMed/NCBI