Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator.

IF 5.7 2区 医学 Q1 Medicine
Guoying Wang, Richard Xu, Boyang Zhang, Xiumei Hong, Tami R Bartell, Colleen Pearson, Liming Liang, Xiaobin Wang
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Abstract

Background: In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population.

Methods: This study included 954 mother-newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package.

Results: 126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%.

Conclusions: In this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth.

宫内暴露于母体糖尿病对早产的影响:胎儿DNA甲基化改变是一个重要的中介。
背景:子宫内暴露于糖尿病已被证明有助于早产,尽管潜在的生物学机制尚未完全阐明。在子宫内建立的胎儿表观遗传变异可能是一个可能的途径。本研究旨在调查子宫内暴露于糖尿病是否与新生儿DNA甲基化变化有关,以及在种族多样化的出生队列人群中,已确定的CpG位点是否介导糖尿病和早产之间的关联。方法:本研究纳入954对母婴。使用Illumina Infinium MethylationEPIC BeadChip 850 K阵列平台测定脐带血中的甲基化水平。子宫内暴露于糖尿病是由母体妊娠期或妊娠期糖尿病的存在来定义的。早产被定义为出生时胎龄少于37周。采用线性回归分析鉴定差异甲基化的CpG位点。使用DMRcate Package鉴定差异甲基化区域。结果:126例(13%)新生儿为妊娠期糖尿病母亲所生,173例(18%)新生儿为早产,41例新生儿为早产和妊娠期糖尿病母亲所生。全基因组CpG分析发现,在FDR阈值为5%时,脐带血中18个CpG位点被母体糖尿病状态差异甲基化。这些重要的CpG位点被定位到12个已知基因,其中一个被注释为基因Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB)。一致地,两个确定的显著甲基化区域之一与HLA-DMB重叠。鉴定出的差异甲基化的CpG位点介导了妊娠期糖尿病和早产之间61%的关联。结论:在这个美国出生队列中,我们发现母亲糖尿病与胎儿DNA甲基化模式改变有关,这在很大程度上解释了糖尿病和早产之间的联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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