scholarly journals Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus

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.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248694
Author(s):  
Stephanie Dias ◽  
Sumaiya Adam ◽  
Yoonus Abrahams ◽  
Paul Rheeder ◽  
Carmen Pheiffer

DNA methylation is increasingly recognized as a potential biomarker of metabolic disease. However, there is limited information on the impact of human immunodeficiency virus (HIV) infection on the candidacy of DNA methylation to serve as molecular biomarkers. This study investigated the effect of HIV infection on DNA methylation patterns in the peripheral blood of South African women with (n = 95) or without (n = 191) gestational diabetes mellitus (GDM). DNA methylation levels at eight CpG sites in the adiponectin gene (ADIPOQ) promoter were measured using bisulfite conversion and pyrosequencing. Differences between HIV negative (-) and positive (+) women were observed. In HIV- women, methylation at CpG -3400 was lower in GDM+ women compared to those with normoglycemia (8.5-fold; p = 0.004), and was associated with higher fasting glucose (β-co-efficient = 0.973; p = 0.006) and lower adiponectin (β-co-efficient = -0.057; p = 0.014) concentrations. These associations were not observed in HIV+ women. In silico analysis showed that Transcription Factor AP2-alpha is able to bind to the altered CpG site, suggesting that CpG -3400 may play a functional role in the regulation of ADIPOQ expression. Our findings show that DNA methylation differs by HIV status, suggesting that HIV infection needs to be taken into consideration in studies exploring DNA methylation as a biomarker of GDM in high HIV prevalence settings.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yoshifumi Kasuga ◽  
Tomoko Kawai ◽  
Kei Miyakoshi ◽  
Yoshifumi Saisho ◽  
Masumi Tamagawa ◽  
...  

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.


2020 ◽  
Vol 24 (23) ◽  
pp. 13899-13912 ◽  
Author(s):  
Weiqiang Zhu ◽  
Yupei Shen ◽  
Junwei Liu ◽  
Xiaoping Fei ◽  
Zhaofeng Zhang ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Barnabas Kahiira Natamba ◽  
Arthur Araali Namara ◽  
Moffat Joha Nyirenda

Abstract Background The burden, determinants and outcomes of gestational diabetes mellitus (GDM) in sub-Saharan Africa are not known. We summarized existing evidence on the prevalence, risk factors and complications of GDM in the region. Methods PubMed was searched from inception to January 31st 2019. Studies were included if carried out in any of the sub-Saharan Africa countries and were available as abstracts or full texts. Interventional studies and those only including qualitative data were excluded. We employed random effects modelling to estimate the pooled GDM prevalence and risk ratios (RRs) for risk factors and outcomes of GDM and their 95%CI. Results 283 papers were identified in the initial search, 33 of which met the inclusion criteria. Data on GDM burden suggest a pooled prevalence of 9% (95%CI, 7–12%). Family history of type 2 diabetes and previous history of GDM, macrosomia, stillbirth and abortion were important risk factors of GDM. In addition, being overweight or obese, over 25 years of age or hypertensive increased the risk of GDM. In terms of complications, GDM more than doubles the risk macrosomia (RR; 95%CI: 2.2; 1.1–4.4). Conclusions There is a high burden of gestational diabetes mellitus in sub-Saharan Africa, but more studies are needed to document locally important risk factors as well as maternal and offspring outcomes. Interventions to reduce obesity among older African women might lead to reduced risk of GDM in sub-Saharan Africa.


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