Genome-wide DNA methylation variation in maternal and cord blood of gestational diabetes population

Kang, Jessica; Lee, Chien‐Nan; Li, Chung‐Yi; Hsu, Kai-Han; Lin, Song

doi:10.1016/j.diabres.2017.07.034

Cited by 48 publications

(56 citation statements)

References 35 publications

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“…One potential mechanism underlying such a diverse array of GDMassociated outcomes is epigenetic dysregulation. In support of this, a growing number of studies have observed associations between GDM and cord blood DNA methylation patterns (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, the majority of studies have been small (e.g., fewer than 100 participants or fewer than 30 GDM cases), adjusted for few if any covariates, and used lenient or no adjustment for multiple testing (8-10, 12-15, 17), which may have contributed to a lack of replication of results across studies.…”

Section: Introductionmentioning

confidence: 80%

Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium

et al. 2019

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OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345–248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870–135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate–adjusted P value threshold of 0.05. CONCLUSIONS Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

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Section: Introductionmentioning

confidence: 80%

Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium

et al. 2019

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“…An increasing number of evidences indicate that deregulation of DNA methylation is involved in pathogenesis of GDM (Shen et al, ). It has been reported that global placental DNA hyper‐methylation is associated with GDM (Kang, Lee, Li, Hsu, & Lin, ).…”

Section: Introductionmentioning

confidence: 99%

Methylation of HIF3A promoter CpG islands contributes to insulin resistance in gestational diabetes mellitus

Zhang

Chen

et al. 2019

Molec Gen & Gen Med

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Background Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance during pregnancy, and will lead to high risk of diabetes even after pregnancy. Hypoxia‐inducible factor (HIF) family proteins are transcriptional factors that are highly correlated with methylation, which might be involved in the regulation of GDM. Methods Baseline clinical characteristics of the GDM patients and healthy women were analyzed. Omental tissue from GDM patients and control groups were collected and detected for the expression levels of HIF1A, HIF2A, and HIF3A. The CpG islands of HIF3A promoter were predicted by “methprimer” software, and the methylation level of CpG islands was detected by bisulfite sequencing PCR. Results HIF3A was downregulated in the omental tissue from GDM patients, whereas HIF1A and HIF2A were not affected. Furthermore, HIF3A expression was positively correlated with levels of estrogen receptor α (ESR1) and solute carrier family 2 member 4 (SLC2A4). Moreover, CpG islands of HIF3A promoter were highly methylated in GDM patients. In addition, methylation level of CpG islands could be upregulated by Estradiol (E2) treatment, since high dose of E2 reduced HIF3A mRNA expression in 3T3‐L1 adipocytes. Conclusion Our findings demonstrate that the expression level of HIF3A, but not HIF1A or HIF2A, is downregulated in GDM patients. The methylation status of HIF3A promoter region is highly correlated with GDM, which could be a novel therapeutic target for GDM treatment.

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“…Interestingly, the changes in methylation status of these genes in whole blood occurred prior to the development of GDM, supporting their potential as screening biomarkers of GDM. In a study investigating maternal and cord blood in pregnant women and their offspring, Kang et al [55] identified 200 genes that were differentially methylated in women with GDM compared with controls. Conversely, our recent study [56] showed no differences in global DNA methylation between pregnant women with GDM and CME those with normoglycaemia in SA.…”

Section: Epigeneticsmentioning

confidence: 99%

Screening and diagnosis of gestational diabetes mellitus in South Africa: What we know so far

2019

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The early detection and management of gestational diabetes mellitus (GDM) present an ideal opportunity to decrease perinatal complications and adverse long-term health outcomes in mothers and their offspring. This review describes the major GDM screening and diagnostic strategies used worldwide, including novel screening and diagnostic methods that are being explored. It highlights the varied screening and diagnostic strategies currently employed in South Africa (SA). The lack of uniform GDM diagnostic criteria and variation in clinical practice hamper early detection and management of GDM, which negatively affects maternal and child health. We recommend that an SA diabetes-in-pregnancy study group, comprising interested obstetricians, physicians, endocrinologists, public health specialists, dieticians and scientists, be established to make evidence-based recommendations on affordable, accessible and applicable GDM screening and diagnostic and management strategies.

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Genome-wide DNA methylation variation in maternal and cord blood of gestational diabetes population

Cited by 48 publications

References 35 publications

Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium

Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium

Methylation of HIF3A promoter CpG islands contributes to insulin resistance in gestational diabetes mellitus

Screening and diagnosis of gestational diabetes mellitus in South Africa: What we know so far

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