Prenatal maternal stress is associated with hypomethylation of the glucocorticoid receptor promoter: the Boston ACCESS study

The role of epigenetic changes in the early life origins of asthma is only beginning to be explored. Prenatal glucocorticoid programming may be one pathway leading to asthma risk. We examined the relationship between prenatal maternal stress and methylation in a CpG-rich area in proximity of the glucocorticoid receptor (GR) promoter region in a sample of 236 women enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a prospective study of early life exposures and childhood asthma risk in an inner-city cohort. The Crisis in Family Systems (CRISYS), a measure of contemporary urban life stressors categorized into specific domains, was administered to mothers before childbirth. Current psychological symptoms were collected using the Edinburgh Depression Scale (EDS) dichotomized using a cutoff >13. Bisulfite-treated genomic DNA from white blood cells was subjected to DNA methylation analysis by quantitative pyrosequencing methods. In bivariate regression analysis increased maternal age (= -0.12, p=0.01), Hispanic race/ethnicity vs. white (= -2.2, p=0.05), life events including financial strain (= -0.22, p=0.05) and home problems (= -0.82, p=0.06) and depression (= -0.9, p=0.10) predicted decreased methylation. In multivariate models, home problems (= -0.83, p=0.05) and the EDS score (= -1.1, p=0.05) were significant when adjusted for maternal age and race. We provide preliminary evidence that prenatal stress and psychological functioning are associated with changes in epigenetic marks in the GR promoter, potentially regulating the receptor expression. How such changes influence asthma risk in offspring warrants further study.