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DNA methylation profiles in sibling pairs discordant for intrauterine exposure to maternal gestational diabetes
Open accessAbstract
Intrauterine exposure to hyperglycemia is reported to confer increased metabolic risk in later life, supporting the 'developmental origins of health and disease' hypothesis. Epigenetic alterations are suggested as one of the possible underlying mechanisms. In this study, we compared pairwise DNA methylation differences between siblings whose intrauterine exposure to maternal gestational diabetes (GDM) were discordant. Methylation of peripheral blood DNA of 18 sibling pairs was measured using Infinium HumanMethylation450 BeadChip assays. Of the 465,447 CpG sites analyzed, 12 showed differential methylation (false discovery rate <0.15), including markers within genes associated with monogenic diabetes (HNF4A) or obesity (RREB1). The overall methylation at HNF4A showed inverse correlations with mRNA expression levels, though non significant. In a gene set enrichment analysis, metabolism and signal transduction pathways were enriched. In conclusion, we found DNA methylation markers associated with intrauterine exposure to maternal GDM, including those within genes previously implicated in diabetes or obesity.
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Twelve differentially methylated regions were discovered that included regions in HNF4A and RREB1 that are associated with monogenic diabetes and obesity, respectively.
“Twelve differentially methylated regions were discovered that included regions in HNF4A and RREB1 that are associated with monogenic diabetes and obesity, respectively.”
From Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications (2022) · cites this paper as [38]
The Differentially methylated CpG sites section reports 12 differentially methylated CpG sites, including one in HNF4A and one in RREB1. The Abstract associates those genes with monogenic diabetes and obesity, respectively. The paper does not report discovering 12 differentially methylated regions; the claim changes the unit of the finding from sites to regions. (LLM, conf=0.88)
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References 47 · Cited by 36
Research works printed but not linked: 1
- Kelstrup L, 2016, Diabetes, db160227
Metadata
- Authors
- Kim, E., Kwak, S. H., Chung, H. R., Ohn, J. H., Bae, J. H., Choi, S. H., Park, K. S., Hong, J.-S., Sung, J., & Jang, H. C.
- Affiliations
- Seoul National University (KR)
- Seoul National University Bundang Hospital (KR)
- Corresponding author
- Jang, Hak Chul
- ORCID
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2017-10-03
- Volume
- 12
- Issue
- 10
- Pages
- 825-832
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC5788413
- OpenAlex
- W2766654256
- Semantic Scholar
- 090c74b26d01a00b94acd05651fecce83f747203
- Cited by
- 36
- References
- 47
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 5 · 2018: 3
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epigenetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI15C3131)
- Seoul National University Hospital (30–2015–0240)
- Seoul National University Bundang Hospital (14–2014–030)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- DNA methylation, gestational diabetes mellitus, intrauterine hyperglycemia, developmental origins of health and disease, sibling discordance, HNF4α, RREB1, monogenic diabetes, obesity, epigenetic modifications, gene expression, metabolic pathways, signal transduction
- MeSH terms
- Adult, Child, Child, Preschool, DNA-Binding Proteins, Female, Fetal Blood, Humans, Hyperglycemia, Male, Obesity, Pregnancy, Transcription Factors, Diabetes, Gestational, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, Siblings, Hepatocyte Nuclear Factor 4, Genome-Wide Association Study, Epigenomics
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