Bioinformatics enrichment analysis of genes and pathways related to maternal type 1 diabetes associated with adverse fetal outcomes

Maternal type 1 diabetes mellitus (T1DM) may affect fetal development by altering the gene expression profile of the umbilical cord. The present study aimed to explore the T1DM-induced gene expression changes in the fetal umbilical cord. The raw gene expression profiles (ID: GSE51546) of umbilical c...

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Bibliographic Details
Published in:Journal of diabetes and its complications 2020-05, Vol.34 (5), p.107556-107556, Article 107556
Main Authors: Bhushan, Ravi, Rani, Anjali, Ali, Akhtar, Singh, Vinay Kumar, Dubey, Pawan K.
Format: Article
Language:English
Subjects:
Apgar score
Bioinformatics
Birth weight
Datasets
Diabetes
Differentially expressed genes
Fetuses
Gene expression
Gene ontology
Gestational age
Glucose
Hyperglycemia
Inflammation
Insulin resistance
Maternal & child health
Maternal diabetes
Metabolism
Mothers
Pregnancy
Principal components analysis
Protein-protein interaction
Proteins
Software
Umbilical cord
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Summary:Maternal type 1 diabetes mellitus (T1DM) may affect fetal development by altering the gene expression profile of the umbilical cord. The present study aimed to explore the T1DM-induced gene expression changes in the fetal umbilical cord. The raw gene expression profiles (ID: GSE51546) of umbilical cord tissue obtained from six normal mothers (non-diabetic) and six type 1 diabetic mothers were used to identify the differentially expressed genes. Genes that correspond to official gene symbols were selected for protein-protein interaction (PPI) and sub-network construction (combined score > 0.4). Functional annotation for Gene Ontology (GO) and pathway enrichment analysis were performed for genes involved in networking. A total of 110 differentially expressed genes were identified of which 38 were up-regulated while 72 were down-regulated. Only 37 genes were identified to significantly interact with each other. Hub genes including HSPA4, KCTD6, UBE2G1, FBXL19, and EHMT1 were up-regulated while KBTBD7, TRIM32, and NUP were down-regulated. T1DM had a major effect on the expression of genes involved in cellular death and differentiation, cell signaling and communication, protein modification and regulation of GTPase activity. Total 27 pathways were enriched and genes related to Wnt signaling, VEGF signaling, inflammation mediated by chemokine and cytokine signaling pathways, FGF signaling pathways and GnRH receptor pathways were found significantly affected by T1DM. Our results suggest that the T1DM environment seems to alter umbilical cord gene expression involved in the regulation of pathophysiology of the diabetic mother which in turn may lead to long-term consequences in various tissues in infants. This study provides insight into the molecular mechanism underlying the adverse pregnancy outcomes of maternal T1DM. •Total 110 DEGs were identified in which 38 were up-regulated while 72 down-regulated.•Total 27 pathways were enriched in which Wnt, VEGF, FGF and GnRH are major pathways and may essential for T1DM.•Hub genes HSPA4, KCTD6, UBE2G1, FBXL19, EHMT1 were up and KBTBD7, TRIM32 and NUP were down -regulated.•T1DM environment alter umbilical cord expression of genes involved in the regulation of pathophysiology of diabetic mother.•This study provides insight into the molecular mechanism underlying the adverse pregnancy outcomes of maternal T1DM.
ISSN:1056-8727
1873-460X
DOI:10.1016/j.jdiacomp.2020.107556