DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm

Abstract

BackgroundPrenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-κB signaling pathway in T cells mediates the effect of objective PNMS on Th1 and Th2 cytokine production in blood from 13½ year olds who were exposed in utero to the 1998 Quebec ice storm.ResultsBootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-κB signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-γ secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction.ConclusionsThe present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0219-0) contains supplementary material, which is available to authorized users.

Pregnant women's cognitive appraisal of a natural disaster affects their children's BMI and central adiposity via DNA methylation: Project Ice Storm

“…A mediating effect, described by Baron and Kenny, is the possible effect of a third variable, intervening in an existing relationship between a predictor and an outcome [17]. Previously, we performed mediation analyses and demonstrated that genome-wide DNA methylation levels mediate the effects of objective stress on children's BMI and waist to height ratio (WHtR), an index of central adiposity [18] and their cytokine secretion levels [19] during adolescence.…”

Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness

“…Furthermore, post-mortem analysis of suicide victims’ hippocampal tissues revealed that a history of childhood abuse was related to greater methylation of NR3C1 as well as the ribosomal ribonucleic acid (RNA) genes 19 , 31 , indicating that DNA methylation changes were also observed in central tissues. Importantly, DNA methylation mediated the impact of early adversity on later health outcomes 32 – 34 .…”

“…Various regulatory regions of the gene were assessed in order to identify key CpG sites sensitive to ELA. Given that methylation mediated the impact of ELA on later health outcomes in animal and human studies 9 , 32 , 33 , a secondary aim of this study was to evaluate the associations between OXTR methylation and childhood trajectories of anxiousness and disruptiveness. Furthermore, given the sexually dimorphic role of oxytocin in social behaviors 57 , sex-specific analyses were also conducted.…”

Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1

“…A link of NR3C1 DNA methylation and altered infant stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis was found in the study of Oberlander et al [ 4 ]. DNA methylation of other candidate genes with a role in HPA axis [ 6 , 9 ] or immune system function [ 10 ] was associated with prenatal stress as well.…”