Epigenome wide association study in peripheral blood of pregnant women identifies potential metabolic pathways related to gestational diabetes

Gestational diabetes mellitus (GDM) increases the risk of developing metabolic disorders in both pregnant women and their offspring. Factors such as nutrition or the intrauterine environment may play an important role, through epigenetic mechanisms, in the development of GDM. The aim of this work is to identify epigenetic marks involved in the mechanisms or pathways related to gestational diabetes. A total of 32 pregnant women were selected, 16 of them with GDM and 16 non-GDM. DNA methylation pattern was obtained from Illumina Methylation Epic BeadChip, from peripheral blood samples at the diagnostic visit (26–28 weeks). Differential methylated positions (DMPs) were extracted using ChAMP and limma package in R 2.9.10, with a threshold of FDR <0.05, deltabeta >|5|% and B >0. A total of 1.141 DMPs were found, and 714 were annotated in genes. A functional analysis was performed, and we found 23 genes significantly related to carbohydrate metabolism. Finally, a total of 27 DMPs were correlated with biochemical variables such as glucose levels at different points of oral glucose tolerance test, fasting glucose, cholesterol, HOMAIR and HbA1c, at different visits during pregnancy and postpartum. Our results show that there is a differentiated methylation pattern between GDM and non-GDM. Furthermore, the genes annotated to the DMPs could be implicated in the development of GDM as well as in alterations in related metabolic variables.

妊娠期糖尿病（Gestational diabetes mellitus, GDM）会提升妊娠女性及其子代罹患代谢紊乱的风险。营养状态或宫内环境等因素可能通过表观遗传机制，在GDM的发生发展中发挥关键调控作用。本研究旨在识别与妊娠期糖尿病相关机制或通路相关的表观遗传标记。
本研究共纳入32名妊娠女性，其中16名确诊为GDM，16名为非GDM对照。在诊断随访时点（孕26~28周）采集外周血样本，通过Illumina甲基化EPIC芯片（Illumina Methylation Epic BeadChip）获取全基因组DNA甲基化模式。
使用R 2.9.10版本中的ChAMP与limma软件包提取差异甲基化位点（Differential methylated positions, DMPs），筛选阈值设置为错误发现率（False Discovery Rate, FDR）<0.05、deltaβ值的绝对值>5%且B值>0。
最终共鉴定出1141个DMPs，其中714个可注释到基因。随后开展功能分析，结果显示共有23个基因与碳水化合物代谢显著相关。
此外，共27个DMPs与多项生化指标存在显著关联，包括妊娠及产后不同随访时点的口服葡萄糖耐量试验各时点血糖、空腹血糖、胆固醇、HOMAIR及糖化血红蛋白（HbA1c）水平。
本研究结果表明，GDM组与非GDM组之间存在显著差异化的甲基化模式。此外，注释到DMPs的基因可能参与GDM的发生发展，以及相关代谢指标的异常改变。