Gender-dependent miR-375 promoter methylation and the risk of type 2 diabetes

Cheng,Jia; Wang,Lingyan; Xu,Leiting; Wang,Hongwei; Liu,Panpan; Bu,Shizhong; Ye,Meng; Zhang,Lina; Wang,Qinwen; Duan,Shiwei

doi:10.3892/etm.2013.1069

June 2013 Volume 5 Issue 6

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June 2013 Volume 5 Issue 6

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Article

Gender-dependent miR-375 promoter methylation and the risk of type 2 diabetes

Authors:
- Jia Cheng
- Lingyan Wang
- Leiting Xu
- Hongwei Wang
- Panpan Liu
- Shizhong Bu
- Meng Ye
- Lina Zhang
- Qinwen Wang
- Shiwei Duan
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Affiliations: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Bank of Blood Products, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China, Section of Endocrinology, The University of Chicago Pritzker School of Medicine, Chicago, IL 60637, USA, Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Department of Endocrinology, The Affiliated Hospital, School of Medicine, Ningbo University, Ningbo, Zhejiang 315000, P.R. China
Pages: 1687-1692
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Published online on: April 18, 2013

https://doi.org/10.3892/etm.2013.1069
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Abstract

Promoter DNA methylation may reflect the interaction between genetic background and environmental factors in the development of metabolic disorders, including type 2 diabetes (T2D). As an epigenetic factor of T2D, miR-375 plays an important role in the functional accommodation of islet cells. In the present study, we investigated the association of promoter DNA methylation of the miR-375 gene with the risk of T2D. Using bisulfite pyrosequencing technology, the DNA methylation levels of eight CpG dinucleotides on the miR-375 promoter were measured in 48 T2D cases and 48 healthy controls. The majority of CpGs (with the exception of CpG7) had significantly higher methylation levels in women compared with those in men (P<0.05). The methylation levels of the eight CpGs were significantly correlated with each other (P<0.001). No significant association between miR-375 gene promoter methylation and the risk of T2D was identified (P=0.417). Similar results were observed in the breakdown analysis by gender (men, P=0.844; women, P=0.234). In addition, although a correlation between the CpG8 methylation level of miR-375 and total triglyceride level was identified in women (P=0.009), DNA methylation of the majority of CpGs in the miR-375 gene promoter was not associated with the clinical metabolic features of the individuals.

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1.	Shantikumar S, Caporali A and Emanueli C: Role of microRNAs in diabetes and its cardiovascular complications. Cardiovasc Res. 93:583–593. 2012. View Article : Google Scholar : PubMed/NCBI
2.	Shaw JE, Sicree RA and Zimmet PZ: Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 87:4–14. 2010. View Article : Google Scholar : PubMed/NCBI
3.	Wild S, Roglic G, Green A, et al: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 27:1047–1053. 2004.PubMed/NCBI
4.	Fernandez-Valverde SL, Taft RJ and Mattick JS: MicroRNAs in β-cell biology, insulin resistance, diabetes and its complications. Diabetes. 60:1825–1831. 2011.
5.	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993.
6.	Wightman B, Ha I and Ruvkun G: Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 75:855–862. 1993. View Article : Google Scholar : PubMed/NCBI
7.	Dehwah MA, Xu A and Huang Q: MicroRNAs and type 2 diabetes/obesity. J Genet Genomics. 39:11–18. 2012. View Article : Google Scholar : PubMed/NCBI
8.	Avnit-Sagi T, Kantorovich L, Kredo-Russo S, et al: The promoter of the pri-miR-375 gene directs expression selectively to the endocrine pancreas. PLoS One. 4:e50332009. View Article : Google Scholar : PubMed/NCBI
9.	Krutzfeldt J and Stoffel M: MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab. 4:9–12. 2006. View Article : Google Scholar : PubMed/NCBI
10.	Poy MN, Hausser J, Trajkovski M, et al: miR-375 maintains normal pancreatic alpha- and beta-cell mass. Proc Natl Acad Sci USA. 106:5813–5818. 2009. View Article : Google Scholar : PubMed/NCBI
11.	Kong L, Zhu J, Han W, et al: Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 48:61–69. 2011. View Article : Google Scholar : PubMed/NCBI
12.	Barres R and Zierath JR: DNA methylation in metabolic disorders. Am J Clin Nutr. 93:897S–900S. 2011. View Article : Google Scholar : PubMed/NCBI
13.	Volkmar M, Dedeurwaerder S, Cunha DA, et al: DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients. EMBO J. 31:1405–1426. 2012. View Article : Google Scholar : PubMed/NCBI
14.	Toperoff G, Aran D, Kark JD, et al: Genome-wide survey reveals predisposing diabetes type 2-related DNA methylation variations in human peripheral blood. Hum Mol Genet. 21:371–383. 2012. View Article : Google Scholar : PubMed/NCBI
15.	Baroukh NN and Van Obberghen E: Function of microRNA-375 and microRNA-124a in pancreas and brain. FEBS J. 276:6509–6521. 2009. View Article : Google Scholar : PubMed/NCBI
16.	World Health Organization: Definition, Diagnosis and Classification of Diabetes mellitus and its Complications; Part 1: Diagnosis and Classification of Diabetes Mellitus. Department of Noncommunicable Disease Surveillance; Geneva: 1999
17.	Bredfeldt TG, Greathouse KL, Safe SH, et al: Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K/AKT. Mol Endocrinol. 24:993–1006. 2010. View Article : Google Scholar : PubMed/NCBI
18.	Li L, Lee KM, Han W, et al: Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer. Hum Mol Genet. 19:4273–4277. 2010. View Article : Google Scholar : PubMed/NCBI
19.	Starlard-Davenport A, Tryndyak VP, James SR, et al: Mechanisms of epigenetic silencing of the Rassf1a gene during estrogen-induced breast carcinogenesis in ACI rats. Carcinogenesis. 31:376–381. 2010. View Article : Google Scholar : PubMed/NCBI
20.	Poy MN, Eliasson L, Krutzfeldt J, et al: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432:226–230. 2004. View Article : Google Scholar : PubMed/NCBI
21.	Ling HY, Wen GB, Feng SD, et al: MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extra-cellular signal-regulated kinase signalling. Clin Exp Pharmacol Physiol. 38:239–246. 2011. View Article : Google Scholar : PubMed/NCBI
22.	Husseiny MI, Kuroda A, Kaye AN, et al: Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes. PLoS One. 7:e479422012. View Article : Google Scholar : PubMed/NCBI
23.	Kuroda A, Rauch TA, Todorov I, et al: Insulin gene expression is regulated by DNA methylation. PLoS One. 4:e69532009. View Article : Google Scholar : PubMed/NCBI
24.	Ekstrom TJ, Lavebratt C and Schalling M: The importance of epigenomic studies in schizophrenia. Epigenomics. 4:359–362. 2012. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Gender-dependent miR-375 promoter methylation and the risk of type 2 diabetes

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Abstract

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