摘要：Ba c k g r o u n d: Epigenetic modifications, such as DNA methyla tion, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear.oB j e c t i v e: We investigated epigenome-wide methyla tion in cord blood of newborns in relation to maternal smoking during pregnancy.Me t h o d s: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methyla tion at 473,844 CpG sites (CpGs) in 1,062 new-born cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethyla tion450 BeadChip (450K).re s u l t s: We found diffe rential DNA methyla tion at epigenome-wide statistical significa nce (p-value < 1.06 × 10–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke.co n c l u s i o n s: We identified a set of genes with methyla tion changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methyla tion across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our find-ings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure
关键词：epigenetics; epigenome-wide; in utero; maternal smoking; methyla ;tion
