DNA methylation of microRNA-375 in impaired glucose tolerance

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.