scholarly journals Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring

2015 ◽  
Vol 24 (11) ◽  
pp. 3021-3029 ◽  
Author(s):  
Sarah Finer ◽  
Chris Mathews ◽  
Rob Lowe ◽  
Melissa Smart ◽  
Sara Hillman ◽  
...  
2017 ◽  
Vol 132 ◽  
pp. 127-136 ◽  
Author(s):  
Jessica Kang ◽  
Chien-Nan Lee ◽  
Hung-Yuan Li ◽  
Kai-Han Hsu ◽  
Shin-Yu Lin

2019 ◽  
Vol 20 (23) ◽  
pp. 5828 ◽  
Author(s):  
Stephanie Dias ◽  
Sumaiya Adam ◽  
Paul Rheeder ◽  
Johan Louw ◽  
Carmen Pheiffer

Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM.


2020 ◽  
Vol 105 (10) ◽  
pp. 3250-3264 ◽  
Author(s):  
Sara E Pinney ◽  
Apoorva Joshi ◽  
Victoria Yin ◽  
So Won Min ◽  
Cetewayo Rashid ◽  
...  

Abstract Context Gestational diabetes (GDM) has profound effects on the intrauterine metabolic milieu and is linked to obesity and diabetes in offspring, but the mechanisms driving these effects remain largely unknown. Alterations in DNA methylation and gene expression in amniocytes exposed to GDM in utero represent a potential mechanism leading to metabolic dysfunction later in life. Objective To profile changes in genome-wide DNA methylation and expression in human amniocytes exposed to GDM. Design A nested case-control study (n = 14 pairs) was performed in amniocytes matched for offspring sex, maternal race/ethnicity, maternal age, gestational age at amniocentesis, and gestational age at birth. Sex-specific genome-wide DNA methylation analysis and RNA-sequencing were completed and differentially methylated regions (DMRs) and gene expression changes were identified. Ingenuity pathway analysis identified biologically relevant pathways enriched after GDM exposure. In silico high-throughput chromosome conformation capture (Hi-C) analysis identified potential chromatin interactions with DMRs. Results Expression of interferon-stimulated genes was increased in GDM amniocytes, accounting for 6 of the top 10 altered genes (q < 0.05). Enriched biological pathways in GDM amniocytes included pathways involving inflammation, the interferon response, fatty liver disease, monogenic diabetes, and atherosclerosis. Forty-two DMRs were identified in male GDM-exposed amniocytes and 20 in female amniocyte analysis (q < 0.05). Hi-C analysis identified interactions between DMRs and 11 genes with significant expression changes in male amniocytes and 9 in female amniocytes (P < .05). Conclusion In a unique repository of human amniocytes exposed to GDM in utero, transcriptome analysis identified enrichment of inflammation and interferon-related pathways and novel DMRs with potential distal regulatory functions.


2016 ◽  
Author(s):  
Patrick De Boever ◽  
Sabine S. Langie ◽  
Matthieu Moisse ◽  
Katarzyna Szarc Vel Szic ◽  
Ellen Van Der Plas ◽  
...  

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Manu J Dubin ◽  
Pei Zhang ◽  
Dazhe Meng ◽  
Marie-Stanislas Remigereau ◽  
Edward J Osborne ◽  
...  

Epigenome modulation potentially provides a mechanism for organisms to adapt, within and between generations. However, neither the extent to which this occurs, nor the mechanisms involved are known. Here we investigate DNA methylation variation in Swedish Arabidopsis thaliana accessions grown at two different temperatures. Environmental effects were limited to transposons, where CHH methylation was found to increase with temperature. Genome-wide association studies (GWAS) revealed that the extensive CHH methylation variation was strongly associated with genetic variants in both cis and trans, including a major trans-association close to the DNA methyltransferase CMT2. Unlike CHH methylation, CpG gene body methylation (GBM) was not affected by growth temperature, but was instead correlated with the latitude of origin. Accessions from colder regions had higher levels of GBM for a significant fraction of the genome, and this was associated with increased transcription for the genes affected. GWAS revealed that this effect was largely due to trans-acting loci, many of which showed evidence of local adaptation.


2014 ◽  
Vol 5 (4) ◽  
pp. 288-298 ◽  
Author(s):  
K. Broberg ◽  
S. Ahmed ◽  
K. Engström ◽  
M. B. Hossain ◽  
S. Jurkovic Mlakar ◽  
...  

Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov–Smirnov test, P-value<10–15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (rS-values>−0.62), but in girls only 207 (41%) showed inverse correlation (rS-values>−0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.


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