Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population.
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.
['Rizzo|Heather E|HE|', 'Escaname|Elia N|EN|', 'Alana|Nicholas B|NB|', 'Lavender|Elizabeth|E|', 'Gelfond|Jonathan|J|0000-0003-1791-0636', 'Fernandez|Roman|R|', 'Hibbs|Matthew A|MA|', 'King|Jonathan M|JM|', 'Carr|Nicholas R|NR|', 'Blanco|Cynthia L|CL|']
D000328:Adult D018899:CpG Islands D019175:DNA Methylation D016640:Diabetes, Gestational D044127:Epigenesis, Genetic D057890:Epigenomics D005260:Female D005312:Fetal Blood D053263:Gene Regulatory Networks D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D006630:Hispanic or Latino D006801:Humans D007231:Infant, Newborn D008423:Maternal Age D008431:Maternal-Fetal Exchange D009765:Obesity D011247:Pregnancy D011446:Prospective Studies D055815:Young Adult
Obesity Diabetes mellitus Newborn DNA methylation Epigenetics Metabolic programming