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

被引：6

作者：

Wang, Guoying ^{[1
]}

Xu, Richard ^{[2
]}

Zhang, Boyang ^{[2
]}

Hong, Xiumei ^{[1
]}

Bartell, Tami R. ^{[3
]}

Pearson, Colleen ^{[4
]}

Liang, Liming ^{[5
,6
]}

Wang, Xiaobin ^{[1
,7
]}

机构：

[1] Johns Hopkins Univ, Ctr Early Life Origins Dis, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[3] Ann & Robert H Lurie Childrens Hosp Chicago, Patrick M Magoon Inst Hlth Communities, Chicago, IL USA

[4] Boston Univ Chobanian, Boston Med Ctr, Avedisian Sch Med, Dept Pediat, Boston, MA USA

[5] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[6] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[7] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD USA

来源：

CLINICAL EPIGENETICS | 2023年 / 15卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Cord blood; Diabetes; DNA methylation; In utero; Preterm birth; CORD BLOOD; HLA-DMA; MELLITUS; GENES; HYPERGLYCEMIA; POLYMORPHISMS; INFLAMMATION; OBESITY; ASTHMA; RISK;

D O I：

10.1186/s13148-023-01473-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundIn 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.MethodsThis 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.Results126 (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%.ConclusionsIn 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.

引用

页数：9

共 50 条

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