Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity

Abstract

ObjectiveFetal exposures may impact offspring epigenetic signatures and adiposity. The authors hypothesized that maternal metabolic traits associate with cord blood DNA methylation, which, in turn, associates with child adiposity.MethodsFasting serum was obtained in 588 pregnant women (27–34 weeks' gestation), and insulin, glucose, high‐density lipoprotein cholesterol, triglycerides, and free fatty acids were measured. Cord blood DNA methylation and child adiposity were measured at birth, 4–6 months, and 4–6 years. The association of maternal metabolic traits with DNA methylation (429,246 CpGs) for differentially methylated probes (DMPs) and regions (DMRs) was tested. The association of the first principal component of each DMR with child adiposity was tested, and mediation analysis was performed.ResultsMaternal triglycerides were associated with the most DMPs and DMRs of all traits tested (261 and 198, respectively, false discovery rate < 0.05). DMRs were near genes involved in immune function and lipid metabolism. Triglyceride‐associated CpGs were associated with child adiposity at 4–6 months (32 CpGs) and 4–6 years (2 CpGs). One, near CD226, was observed at both timepoints, mediating 10% and 22% of the relationship between maternal triglycerides and child adiposity at 4–6 months and 4–6 years, respectively.ConclusionsDNA methylation may play a role in the association of maternal triglycerides and child adiposity.

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

“…Role of Epigenetic Programming in Immune Cells from Offspring Exposed to WSD Epigenetic changes due to maternal diet/obesity can occur throughout neonatal tissues and cells with lasting impact on neonatal development and beyond. Recent studies have shown that cord blood DNA methylation in neonates born to mothers with obesity correlated with maternal triglycerides and childhood adiposity [196]. In NHP studies, both HSPCs and bone marrow-derived macrophages (BMDM) from maternal WSD-exposed 3-year-old offspring were epigenetically modified to a more proinflammatory signature [6], despite weaning at 7 months to a normal chow diet.…”

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