Wang Xiaoli, Chang Xiangyun, Li Jun, Yin Liang, Sun Kan
Departments of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, P.R. China.
Exp Ther Med. 2014 Sep;8(3):775-780. doi: 10.3892/etm.2014.1816. Epub 2014 Jun 30.
In the present study, the expression levels and DNA methylation status of ()-375 in patients with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were analyzed and the role of DNA methylation of in the pathogenesis of T2DM was investigated. Compared with the levels in patients with normal glucose tolerance (NGT; n=53), the samples from patients with IGT (n=44) exhibited downregulation of , while those from patients with T2DM (n=54) exhibited upregulation of 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 promoter was hypermethylated and the levels of in the plasma were downregulated in the patients with IGT. DNA hypomethylation may have an important role in the regulation of expression and may contribute to the pathogenesis of T2DM.
在本研究中,分析了糖耐量受损(IGT)患者和2型糖尿病(T2DM)患者中()-375的表达水平和DNA甲基化状态,并研究了其DNA甲基化在T2DM发病机制中的作用。与糖耐量正常(NGT;n = 53)患者的水平相比,IGT患者(n = 44)的样本显示血浆中()下调,而T2DM患者(n = 54)的样本显示血浆中()上调。此外,与T2DM患者和NGT患者的样本相比,IGT患者的样本被观察到存在高甲基化(P = 0.042)。对17个CpG位点(相对于转录起始位点在-990至-1258 bp之间)中的三个CpG单元(CpG1.2、CpG20和CpG25.26.27)进行分析发现,与NGT患者相比,IGT患者的甲基化水平更高(P < 0.05)。IGT患者中两个CpG单元(CpG1.2和CpG25.26.27)的甲基化高于T2DM患者(P < 0.05)。因此,本研究表明IGT患者中()启动子发生高甲基化,血浆中()水平下调。DNA低甲基化可能在()表达调控中起重要作用,并可能有助于T2DM的发病机制。