Prenatal maternal anxiety promotes atopic dermatitis in offspring via placental DNA methylation changes.

BACKGROUND: Maternal anxiety during pregnancy has been previously reported to be associated with atopic dermatitis (AD) in offspring. The potential mechanism is not yet proven but epigenetic change may be suggested. OBJECTIVE: We examined whether maternal anxiety during pregnancy may alter placental DNA methylation, then develop AD in the offspring. METHODS: We evaluated maternal anxiety at 36 weeks of gestation by self-reported questionnaires, the State-Trait Anxiety Inventory-Trait subscale (STAI-T), in the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) study. AD was diagnosed at 6 months of age by pediatric allergists. We stratified the subjects into four groups according to the STAI score of mothers and diagnosis of AD in children. Placental genome-wide methylation microarray was analyzed using Infinium 450K BeadChip and selected genes were validated by pyrosequencing. RESULTS: From microarray, several differential methylation sites were identified in AD and healthy subjects and in total subjects, regarding to the STAI scores. Among differential methylation sites in microarray, six sites were selected for pyrosequencing. And site of matrix metalloproteinases 27 (MMP27) among 6 sites showed decreased methylation in AD infants with high STAI mothers compared to healthy infants with low STAI mothers. CONCLUSIONS: Epigenetic change in placenta can be a suggesting mechanism for the development of AD in offspring at 6 months of age associated with maternal anxiety during pregnancy and MMP27 may be a candidate gene.