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. 2020 Feb 19;12(1):34.
doi: 10.1186/s13148-020-0824-9.

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

Heather E Rizzo  1 , Elia N Escaname  2   3 , Nicholas B Alana  1   3 , Elizabeth Lavender  2   3 , Jonathan Gelfond  3 , Roman Fernandez  3 , Matthew A Hibbs  1 , Jonathan M King  4 , Nicholas R Carr  5 , Cynthia L Blanco  2   3
Affiliations

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

Heather E Rizzo et al. Clin Epigenetics. .

Abstract

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.

Keywords: DNA methylation; Diabetes mellitus; Epigenetics; Metabolic programming; Newborn; Obesity.

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Conflict of interest statement

The authors declare that they have no competing interests. The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the US Army Medical Department, the US Army Office of the Surgeon General, the Department of the Air Force and Army, Department of Defense or the US Government.

Figures

Fig. 1
Fig. 1
Scatter plots showing the beta value of the top 10 significantly methylated probes found by comparison between diabetic and non-diabetic groups using linear regression and empirical Bayes statistics for differential expression
See this image and copyright information in PMC

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