DNA methylation and gene expression of TXNIP in adult offspring of women with diabetes in pregnancy

Abstract

BackgroundFetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM), possibly mediated by epigenetic mechanisms. Low blood TXNIP DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle TXNIP gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT) and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action. The extent to which TXNIP DNA methylation levels are decreased and/or gene expression levels increased in SAT or skeletal muscle of a developmentally programmed at-risk population is unknown.Objective and methodsThe objective of this study was to investigate TXNIP DNA methylation and gene expression in SAT and skeletal muscle, and DNA methylation in blood, from adult offspring of women with gestational diabetes (O-GDM, n = 82) or type 1 diabetes (O-T1DM, n = 67) in pregnancy compared with offspring of women from the background population (O-BP, n = 57).ResultsSAT TXNIP DNA methylation was increased (p = 0.032) and gene expression decreased (p = 0.001) in O-GDM, but these differences were attenuated after adjustment for confounders. Neither blood/muscle TXNIP DNA methylation nor muscle gene expression differed between groups.ConclusionWe found no evidence of decreased TXNIP DNA methylation or increased gene expression in metabolic target tissues of offspring exposed to maternal diabetes. Further studies are needed to confirm and understand the paradoxical SAT TXNIP DNA methylation and gene expression changes in O-GDM subjects.

Gestational Diabetes Mellitus Affects Offspring’s Epigenome. Is There a Way to Reduce the Negative Consequences?

“…Increased TXNIP expression was shown to inhibit insulin-mediated glucose uptake in skeletal muscle and adipocytes. However, in this study, no changes were observed in the muscles [64]. It should also be mentioned that valuable data can be extracted from the Danish National Birth Cohort (dnbc.dk).…”

Integrated DNA methylation and gene expression analysis in the pathogenesis of coronary artery disease

“…We carried out correlation analysis to detect whether DNA methylation causes CAD by regulating gene expression. The addition of methyl groups at cytosine-guanine dinucleotides (CpGs) in regulatory/promoter regions in DNA, known as DNA methylation, typically leads to transcriptional repression and decreased expression of the gene in question [ 6 ]. However, the DNA methylation was positively correlated with the gene expression in BDNF, IL-6 and PIK3R1.…”

Identification of hub‐methylated differentially expressed genes in patients with gestational diabetes mellitus by multi‐omic WGCNA basing epigenome‐wide and transcriptome‐wide profiling

“…Methylation of the DNA promoter region regulates its expression by leading to transcriptionally silencing. It has been demonstrated that abnormal DNA methylation level is involved in GDM pathogenesis . Thus, methylation data from GSE70494 data set were used to analyze the methylation levels of hub genes between GDM and health samples.…”