暴露于妊娠糖尿病（GDM）会改变胎盘和胎儿脐血中的 DNA 甲基化。

Exposure to Gestational Diabetes Mellitus (GDM) alters DNA methylation in placenta and fetal cord blood.

机构信息

Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.

Head of Molecular Genomics, Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

出版信息

Diabetes Res Clin Pract. 2021 Apr;174:108690. doi: 10.1016/j.diabres.2021.108690. Epub 2021 Feb 5.

DOI:10.1016/j.diabres.2021.108690

PMID:33549677

Abstract

BACKGROUND

Fetal exposure to maternal GDM increases offspring risk for adult-onset metabolic syndromes. Epigenetic modifications such as DNA methylation are modulators for fetal metabolic programming and susceptibility to adult-onset disease. This study investigates genome-wide DNA methylation in GDM exposed cord blood and placenta.

METHODS

Oral glucose tolerance testing between 24 and 28 weeks of pregnancy was used to determine severity of glucose intolerance. We measured DNA methylation (DNAm) using the Illumina Infinium 450 K array in 42 fetal cord blood and 36 placenta samples.

RESULTS

We identified 662 and 99 CpG sites in GDM placenta and cord blood, respectively at p-value <0.01 and a methylation difference >5% after adjustment for confounders. Annotated sites for AHRR and PTPRN2 were common to cord blood and placenta. Adding published GDM cord blood DNAm data we segregated patients based on treatment (Diet Only vs. +Insulin) and identified altered CpG sites to be unique to each GDM treatment group.

CONCLUSION

Consistency in findings with other studies provides evidence for the role of DNAm in placental and fetal responses to hyperglycemia. However, segregating DNAm analysis of GDM samples based on treatment may help delineate whether observed DNAm alterations are reflective of adaptive responses or treatment effects in utero.

摘要

背景

胎儿在母体中暴露于 GDM（妊娠期糖尿病）会增加其成年后患代谢综合征的风险。表观遗传修饰，如 DNA 甲基化，是胎儿代谢编程和成年后易患疾病的调节剂。本研究调查了 GDM 暴露的脐带血和胎盘的全基因组 DNA 甲基化。

方法

在妊娠 24 至 28 周之间进行口服葡萄糖耐量试验，以确定葡萄糖耐量的严重程度。我们使用 Illumina Infinium 450K 阵列测量了 42 例胎儿脐带血和 36 例胎盘样本中的 DNA 甲基化（DNAm）。

结果

我们在 GDM 胎盘和脐带血中分别鉴定出了 662 个和 99 个 CpG 位点，其 p 值均小于 0.01，且在调整混杂因素后，甲基化差异大于 5%。AHRR 和 PTPRN2 的注释位点在脐带血和胎盘中均为常见。在添加已发表的 GDM 脐带血 DNAm 数据后，我们根据治疗（仅饮食与+胰岛素）对患者进行了分类，并发现改变的 CpG 位点是 GDM 治疗组所特有的。