DNA methylation of microRNA‑375 in impaired glucose tolerance

Wang,Xiaoli; Chang,Xiangyun; Li,Jun; Yin,Liang; Sun,Kan

doi:10.3892/etm.2014.1816

DNA methylation of microRNA‑375 in impaired glucose tolerance

Authors:
- Xiaoli Wang
- Xiangyun Chang
- Jun Li
- Liang Yin
- Kan Sun
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Affiliations: Departments of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, P.R. China
Published online on: June 30, 2014 https://doi.org/10.3892/etm.2014.1816
Pages: 775-780

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Abstract

In the present study, the expression levels and DNA methylation status of microRNA (miRNA)‑375 in patients with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were analyzed and the role of DNA methylation of miRNA‑375 in the pathogenesis of T2DM was investigated. Compared with the miR‑375 levels in patients with normal glucose tolerance (NGT; n=53), the samples from patients with IGT (n=44) exhibited downregulation of miR‑375, while those from patients with T2DM (n=54) exhibited upregulation of miR‑375 in the plasma. Additionally, the samples from patients with IGT were observed to be hypermethylated compared with those from patients with T2DM and NGT (P=0.042). Analysis of three CpG units (CpG1.2, CpG20 and CpG25.26.27) from 17 CpG sites (between -990 and ‑1,258 bp, relative to the transcription start site) revealed higher methylation levels in patients with IGT compared with those in patients with NGT (P<0.05). The methylation of two CpG units (CpG1.2 and CpG25.26.27) was higher in patients with IGT than in the patients with T2DM (P<0.05). Thus, the present study demonstrated that the miR‑375 promoter was hypermethylated and the levels of miR‑375 in the plasma were downregulated in the patients with IGT. DNA hypomethylation may have an important role in the regulation of miR‑375 expression and may contribute to the pathogenesis of T2DM.

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