DNA Methylation in Gestational Diabetes and its Predictive Value for Postpartum Glucose Disturbances

Ballesteros, Mónica; Gil-Lluís, Pilar; Ejarque, Miriam; Diaz-Perdigones, Cristina; Martinez-Guasch, Laia; Fernández‐Veledo, Sonia; Ortega, Joan Vendrell; Megía, Ana

doi:10.1210/clinem/dgac462

Cited by 11 publications

(5 citation statements)

References 57 publications

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“…An increasing number of studies suggest that environmental factors are associated with epigenetic marks and that those marks may be important to understand interactions between genetics and environmental factors. A few EWAS of GDM in maternal peripheral blood are published so far, but the data is not sufficient for an MRS for GDM due to heterogeneity in diagnosis criteria used as well as their small sample sizes [28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation risk score for type 2 diabetes is associated with gestational diabetes

Linares-Pineda,

Fragoso-Bargas,

Picón

et al. 2024

Cardiovasc Diabetol

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Background Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria. Methods In two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM. Results With mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1–1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1–1.7], P = 0.00014 for a model adjusted by age, pre-pregnant BMI, family history of diabetes and smoking status. Also, we found 6 CpGs through a meta-analysis (cg14020176, cg22650271, cg14870271, cg27243685, cg06378491, cg25130381) associated with GDM, and some of their methylation quantitative loci (mQTLs) were related to T2DM and GDM. Conclusion For the first time, we show that DNA methylation marks for T2DM are also associated with GDM, suggesting shared epigenetic mechanisms between GDM and T2DM.

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Section: Discussionmentioning

confidence: 99%

DNA methylation risk score for type 2 diabetes is associated with gestational diabetes

Linares-Pineda,

Fragoso-Bargas,

Picón

et al. 2024

Cardiovasc Diabetol

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“…Our results agree with recent studies. Ballesteros et al [ 17 ] identified 3 DMPs within LINC00917 , TRAPPC9, and LEF1 genes in GDM women with abnormal glucose tolerance, and also LINC00917 and TRAPPC9 were associated with abnormal glucose levels after 4 years of postpartum. In another study, carried out in maternal blood before the GDM diagnosis, they found five DMPs in COPS8, PIK3R5, HAAO, CCDC124, and C5orf34 genes with the potential to be clinical biomarkers of GDM development [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another study on peripheral blood of GDM vs. non-GDM presented five CpGs within COP9 signalosome Subunit 8 ( COPS8 ), Phosphoinositide-3-Kinase Regulatory ( PIK3R ), 3-Hydroxyanthranilate 3,4- Dioxygenase ( HAAO ), Coiled-Coil Domain Containing 124 ( CCDC124 ) and Chromosome 5 Open Reading Frame 34 ( C5orf34 ) with biomarker potential for early therapeutic intervention [ 16 ]. Also, a recent study in peripheral blood identified three CpGs in Long Intergenic Non-Protein Coding RNA 917 ( LINC00917 ), Trafficking Protein Particle Complex Subunit 9 ( TRAPPC9 ) and Lymphoid Enhancer Binding Factor 1 ( LEF1 ) genes, respectively, that may be implicated in the development of GDM and postpartum abnormal glucose tolerance [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Epigenome wide association study in peripheral blood of pregnant women identifies potential metabolic pathways related to gestational diabetes

Linares-Pineda,

Peña-Montero,

Gutiérrez-Repiso

et al. 2023

Epigenetics

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Gestational diabetes mellitus (GDM) increases the risk of developing metabolic disorders in both pregnant women and their offspring. Factors such as nutrition or the intrauterine environment may play an important role, through epigenetic mechanisms, in the development of GDM. The aim of this work is to identify epigenetic marks involved in the mechanisms or pathways related to gestational diabetes. A total of 32 pregnant women were selected, 16 of them with GDM and 16 non-GDM. DNA methylation pattern was obtained from Illumina Methylation Epic BeadChip, from peripheral blood samples at the diagnostic visit (26–28 weeks). Differential methylated positions (DMPs) were extracted using ChAMP and limma package in R 2.9.10, with a threshold of FDR <0.05, deltabeta >|5|% and B >0. A total of 1.141 DMPs were found, and 714 were annotated in genes. A functional analysis was performed, and we found 23 genes significantly related to carbohydrate metabolism. Finally, a total of 27 DMPs were correlated with biochemical variables such as glucose levels at different points of oral glucose tolerance test, fasting glucose, cholesterol, HOMAIR and HbA1c, at different visits during pregnancy and postpartum. Our results show that there is a differentiated methylation pattern between GDM and non-GDM. Furthermore, the genes annotated to the DMPs could be implicated in the development of GDM as well as in alterations in related metabolic variables.

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“…More recently, the ability of differentially methylated CpG sites to aid in the prediction of women who will progress to abnormal glucose tolerance in the post-partum period was reported [ 109 ]. An eWAS was performed in a discovery cohort of 24 women with GDM and 24 controls using DNA from blood collected between 26 and 30 weeks of gestation.…”

Section: Gdm and Epigeneticsmentioning

confidence: 99%

Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes

Lowe

2023

IJMS

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Gestational diabetes (GDM) is one of the most common complications of pregnancy, affecting as many as one in six pregnancies. It is associated with both short- and long-term adverse outcomes for the mother and fetus and has important implications for the life course of affected women. Advances in genetics and epigenetics have not only provided new insight into the pathophysiology of GDM but have also provided new approaches to identify women at high risk for progression to postpartum cardiometabolic disease. GDM and type 2 diabetes share similarities in their pathophysiology, suggesting that they also share similarities in their genetic architecture. Candidate gene and genome-wide association studies have identified susceptibility genes that are shared between GDM and type 2 diabetes. Despite these similarities, a much greater effect size for MTNR1B in GDM compared to type 2 diabetes and association of HKDC1, which encodes a hexokinase, with GDM but not type 2 diabetes suggest some differences in the genetic architecture of GDM. Genetic risk scores have shown some efficacy in identifying women with a history of GDM who will progress to type 2 diabetes. The association of epigenetic changes, including DNA methylation and circulating microRNAs, with GDM has also been examined. Targeted and epigenome-wide approaches have been used to identify DNA methylation in circulating blood cells collected during early, mid-, and late pregnancy that is associated with GDM. DNA methylation in early pregnancy had some ability to identify women who progressed to GDM, while DNA methylation in blood collected at 26–30 weeks gestation improved upon the ability of clinical factors alone to identify women at risk for progression to abnormal glucose tolerance post-partum. Finally, circulating microRNAs and long non-coding RNAs that are present in early or mid-pregnancy and associated with GDM have been identified. MicroRNAs have also proven efficacious in predicting both the development of GDM as well as its long-term cardiometabolic complications. Studies performed to date have demonstrated the potential for genetic and epigenetic technologies to impact clinical care, although much remains to be done.

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DNA Methylation in Gestational Diabetes and its Predictive Value for Postpartum Glucose Disturbances

Cited by 11 publications

References 57 publications

DNA methylation risk score for type 2 diabetes is associated with gestational diabetes

DNA methylation risk score for type 2 diabetes is associated with gestational diabetes

Epigenome wide association study in peripheral blood of pregnant women identifies potential metabolic pathways related to gestational diabetes

Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes

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