DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm.
|Title||DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Cao-Lei L, Veru F, Elgbeili G, Szyf M, Laplante DP, King S|
|Keywords||Adolescent, Cohort Studies, CpG Islands, Cytokines, DNA Methylation, Epigenesis, Genetic, Female, Humans, Maternal Exposure, Pregnancy, Prenatal Exposure Delayed Effects, Signal Transduction, Stress, Psychological|
BACKGROUND: Prenatal 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.RESULTS: Bootstrapping 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.CONCLUSIONS: The 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.
|Alternate Journal||Clin Epigenetics|
|PubMed Central ID||PMC4866030|
|Grant List||/ / Canadian Institutes of Health Research / Canada|