ArticleJCI insight2017
Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Effect of maternal diabetes on fetal heart function on echocardiography: systematic review and meta-analysis.Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology · 2021Pooled it
- Maternal obesity and metabolic disorders associate with congenital heart defects in the offspring: A systematic review.PloS one · 2021Pooled it
- Congenital heart defects: familial recurrence patterns in Sweden.European heart journal · 2026Article
- Haploinsufficiency of Endothelial Nitric Oxide Synthase Mitigates Beneficial Effects of Maternal Exercise on Fetal Heart Development During Pregestational Diabetes.Journal of the American Heart Association · 2026Article
- Decoding structural birth defects through genomic landscapes: Innovative frameworks for diagnosis (Review).International journal of molecular medicine · 2026Review
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- Genetics of Congenital Heart Disease: A Narrative Review of Challenges and Strategies in Identifying Novel Genes.Cureus · 2025Review
- Distinct specificity and functions of PRC2 subcomplexes in human stem cells and cardiac differentiation.Molecular cell · 2025Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Macromolecular interactions dictate Polycomb-mediated epigenetic repression.bioRxiv : the preprint server for biology · 2025Article
- The Role of miRNA Expression in Congenital Heart Disease: Insights into the Mechanisms and Biomarker Potential.Children (Basel, Switzerland) · 2025Review
- Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects.Journal of the American Heart Association · 2025Article
- Decoding congenital heart disease: a multi-omic framework for cardiac lineage and regulatory dysfunction.Frontiers in cell and developmental biology · 2025Review
- Genetic and Environmental Contributors To Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2025Review
- Impact of genetic factors on antioxidant rescue of maternal diabetes-associated congenital heart disease.JCI insight · 2024Article
- NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.Nature communications · 2024Article
- Congenital heart defects and consanguinity: An analysis of the Sidra cardiac registry data in Qatar.International journal of cardiology. Congenital heart disease · 2024Article
- NovelGenes · 2024Article
- Association of congenital heart defects (CHD) with factors related to maternal health and pregnancy in newborns in Puerto Rico.Congenital heart disease · 2024Article
- Updating an Overview of Teratology.Methods in molecular biology (Clifton, N.J.) · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Birth defects are the leading cause of infant mortality, and they are caused by a combination of genetic and environmental factors. Environmental risk factors may contribute to birth defects in genetically susceptible infants by altering critical molecular pathways during embryogenesis, but experimental evidence for gene-environment interactions is limited. Fetal hyperglycemia associated with maternal diabetes results in a 5-fold increased risk of congenital heart disease (CHD), but the molecular basis for this correlation is unknown. Here, we show that the effects of maternal hyperglycemia on cardiac development are sensitized by haploinsufficiency of Notch1, a key transcriptional regulator known to cause CHD. Using ATAC-seq, we found that hyperglycemia decreased chromatin accessibility at the endothelial NO synthase (Nos3) locus, resulting in reduced NO synthesis. Transcription of Jarid2, a regulator of histone methyltransferase complexes, was increased in response to reduced NO, and this upregulation directly resulted in inhibition of Notch1 expression to levels below a threshold necessary for normal heart development. We extended these findings using a Drosophila maternal diabetic model that revealed the evolutionary conservation of this interaction and the Jarid2-mediated mechanism. These findings identify a gene-environment interaction between maternal hyperglycemia and Notch signaling and support a model in which environmental factors cause birth defects in genetically susceptible infants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.