Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies

Wu, Pensée; Farrell, William E.; Haworth, Kim E.; Emes, Richard D.; Kitchen, Mark; Glossop, John R; Hanna, Fahmy; Fryer, Anthony A.

doi:10.1080/15592294.2016.1166321

Cited by 59 publications

(61 citation statements)

References 47 publications

(1 reference statement)

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“…A study of DNA methylation in adipose tissue from subjects with type II diabetes and obesity, using the 450K Illumina beadchip, identified HOOK2 as significantly differentially methylated from the healthy group, although their findings indicated that HOOK2 was hypermethylated while our results show the genes being hypomethylated [39]. In an additional DNA methylation study on mothers with gestational diabetes, HOOK2 was found to be commonly differentially methylated in the maternal blood, placenta, and umbilical cord [40].…”

Section: Regional Association Study (Dm)contrasting

confidence: 68%

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population

et al. 2020

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Background: Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population. Methods: Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites. Results: Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22. Conclusions: The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.

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Section: Regional Association Study (Dm)contrasting

confidence: 68%

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population

et al. 2020

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“…However, sprC is involved in cell motility, and may play an important role in the process of bacteria penetrating the mucus lining of the colon 29,30 . HAAO may participate in tryptophan metabolism and the synthesis of quinolinic acid leading to inflammatory disorders and insulin resistance 31,32 . gbcA in bacteria is related to glycine betaine which is an intermediate in the catabolism of choline and carnitine 33 .…”

Section: Discussionmentioning

confidence: 99%

Implication of the gut microbiome composition of type 2 diabetic patients from northern China

Chang

Zhang

et al. 2020

Sci Rep

120

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Emerging evidence has suggested the association of the gut microbiome with some human diseases, including type 2 diabetes (T2D). In this study, we analyzed the gut microbiota from a cohort of healthy and diabetic Chinese individuals from Northern China. Pyrosequencing of the V4V5 region of 16S rRNA genes revealed a significant decrease in the gut microbiota diversity of diabetic patients as compared to healthy individuals. Butyrate-producing bacteria such as Bifidobacterium and Akkermansia were significantly decreased in diabetic patients. Furthermore, the abundance of Dorea was significantly increased in T2D individuals and negatively correlated with the abundance of butyrate-producing bacteria. The increase of Dorea could play a role in the development of T2D and has been previously overlooked. Importantly, functional analysis of the gut microbiome revealed for the first time that increased levels of butyrate production via transferases and the degradation of several amino acids due to gut microbial metabolism have strong correlations with T2D in Northern China. Moreover, the potential of gut microbiota-based classifiers to identify individuals with a high risk for T2D has been demonstrated in this study. Taken together, our findings have revealed a previously unappreciated association of the gut microbiome with T2D and have also suggested that changes in gut microbiota may be used to identify individuals at high risk for T2D.

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“…These studies suggest an early pathogenesis for fetal intolerance that can be detected by screening prior to labor. Previous studies have also reported associations between DNA methylation and pregnancy complications, including preeclampsia and gestational diabetes [16,17]. DNA methylation, the addition of a methyl group to the 5' position of cytosine in a cytosine-guanine dinucleotide (CpG site), serves as a mechanism to regulate gene expression.…”

Section: Introductionmentioning

confidence: 99%

SLC9B1 methylation predicts fetal intolerance of labor

et al. 2018

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Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24-32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18-36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value <8.9 × 10, FDR <0.05) in gene SLC9B1, a Na/H exchanger, were associated with fetal intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.

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Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies

Abstract: Abbreviations 21 DNA

Cited by 59 publications

References 47 publications

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population

Implication of the gut microbiome composition of type 2 diabetic patients from northern China

SLC9B1 methylation predicts fetal intolerance of labor

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