Montasser May E, Cheng Yu-Ching, Tanner Keith, Shuldiner Alan R, O'Connell Jeffrey R
Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA.
J Clin Epigenet. 2017;3(2). doi: 10.21767/2472-1158.100052. Epub 2017 Jun 16.
Type 2 Diabetes (T2D) is a common chronic disease with substantial disease burden and economic impact. Lifestyle changes can significantly alter the course of the disease, if detected at an early stage. DNA methylation signature may serve as a biomarker for early detection of increased T2D risk.
DNA methylation profiling was performed using the Illumina Infinium Human Methylation 450K Bead chip array in 24 normoglycemic Old Order Amish (OOA) individuals who later developed Impaired Fasting Glucose (IFG) (cases), and 24 OOA individuals who remained normoglycemic after an average follow up of 10 years (controls). Cases and controls were matched on age, sex, BMI, baseline fasting glucose, and glucose level after 2 h from 75 g Oral Glucose Tolerance Test (OGTT).
Association analysis found no significant difference in either global methylation or individual probe methylation between cases and controls, however, the top 34 suggestive significant sites were located in genes with interesting biological links to T2D and glycemic traits. These genes include that plays a role in pancreatic cell proliferation and insulin secretion, a known bone mineral density gene that was recently found to be associated also with T2D and glycemic traits, and may explain the link between T2D and BMD, and and both of which are part of insulin signaling pathway.
These results may shed light on the initiation and development of hyperglycemia and T2D and help to identify high risk individuals for early intervention; however, further studies are required for validation.
2型糖尿病（T2D）是一种常见的慢性疾病，具有重大的疾病负担和经济影响。如果在早期阶段被检测到，生活方式的改变可以显著改变疾病的进程。DNA甲基化特征可能作为早期检测T2D风险增加的生物标志物。
使用Illumina Infinium Human Methylation 450K Bead芯片阵列对24名血糖正常的老派阿米什人（OOA）个体进行DNA甲基化分析，这些个体后来发展为空腹血糖受损（IFG）（病例组），以及24名OOA个体，他们在平均随访10年后仍保持血糖正常（对照组）。病例组和对照组在年龄、性别、体重指数、基线空腹血糖以及75克口服葡萄糖耐量试验（OGTT）后2小时的血糖水平方面进行了匹配。
关联分析发现病例组和对照组在整体甲基化或单个探针甲基化方面均无显著差异，然而，前34个提示性显著位点位于与T2D和血糖特征具有有趣生物学联系的基因中。这些基因包括在胰腺细胞增殖和胰岛素分泌中起作用的 ，一个已知的骨密度基因，最近发现它也与T2D和血糖特征有关，可能解释了T2D与骨密度之间的联系，以及 和 ，它们都是胰岛素信号通路的一部分。
这些结果可能有助于揭示高血糖和T2D的发生和发展，并有助于识别高危个体以便进行早期干预；然而，需要进一步研究进行验证。
