Yin Liang, Cai Wei-Juan, Chang Xiang-Yun, Li Jun, Zhu Ling-Yun, Su Xiang-Hui, Yu Xue-Feng, Sun Kan
Department of Endocrinology and Metabolism, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technolog, Wuhan, Hubei.
Department of Clinical Laboratory, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Medicine (Baltimore). 2018 Dec;97(49):e13513. doi: 10.1097/MD.0000000000013513.
Phosphatase and tension homolog deleted on chromosome 10 (PTEN) was considered as a promising target in type 2 diabetes mellitus (T2DM) because of its negative effects on insulin resistance. Alteration in DNA methylation is thought to play a role in the pathogenesis of T2DM. The aim of the present study was to quantitatively evaluate the promoter methylation of PTEN in Uyghur patients with mild T2DM. We evaluated methylation levels in 21 CpG sites from -2515 bp to -2186 bp relative to the translation initiation site in 55 cases of T2DM and 50 cases of normal glucose tolerance (NGT) using the MassARRAY spectrometry. In addition, PTEN mRNA and protein levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting to determine whether DNA methylation alterations were responsible for PTEN expression. Compared with NGT groups, the PTEN mRNA expression was significantly higher in Uyghur patients with mild T2DM groups. We also showed that PTEN protein expression was upregulated in Uyghur patients with mild T2DM groups, but the level of protein kinase B (AKT) was downregulated. PTEN methylation in T2DM patients was significantly lower than that in NGT groups. In addition, 2 CpG units demonstrated a significant difference between the NGT and Uyghur patients with mild T2DM groups. Furthermore, there was a negative association between promoter methylation and PTEN expression. Together, these findings suggest that epigenetic inactivation of PTEN plays an important role in Uyghur patients with mild T2DM. The aberrant methylation of CpG sites within the PTEN promoter may serve as a potential candidate biomarker for T2DM in the Uyghur population.
10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）因其对胰岛素抵抗的负面影响，被视为2型糖尿病（T2DM）的一个有前景的靶点。DNA甲基化改变被认为在T2DM的发病机制中起作用。本研究的目的是定量评估轻度T2DM维吾尔族患者中PTEN的启动子甲基化情况。我们使用MassARRAY质谱分析法评估了55例T2DM患者和50例糖耐量正常（NGT）者中相对于翻译起始位点从-2515 bp至-2186 bp的21个CpG位点的甲基化水平。此外，通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法测量PTEN mRNA和蛋白水平，以确定DNA甲基化改变是否与PTEN表达有关。与NGT组相比，轻度T2DM维吾尔族患者组中PTEN mRNA表达显著更高。我们还表明，轻度T2DM维吾尔族患者组中PTEN蛋白表达上调，但蛋白激酶B（AKT）水平下调。T2DM患者的PTEN甲基化显著低于NGT组。此外，2个CpG单元在NGT组和轻度T2DM维吾尔族患者组之间存在显著差异。此外，启动子甲基化与PTEN表达之间存在负相关。总之，这些发现表明PTEN的表观遗传失活在轻度T2DM维吾尔族患者中起重要作用。PTEN启动子内CpG位点的CpG位点异常甲基化可能作为维吾尔族人群T2DM的潜在候选生物标志物。
