Presence of an epigenetic signature of prenatal cigarette smoke exposure in childhood

Abstract

Prenatal exposure to tobacco smoke has lifelong health consequences. Epigenetic signatures such as differences in DNA methylation (DNAm) may be a biomarker of exposure and, further, might have functional significance for how in utero tobacco exposure may influence disease risk. Differences in infant DNAm associated with maternal smoking during pregnancy have been identified. Here we assessed whether these infant DNAm patterns are detectible in early childhood, whether they are specific to smoking, and whether childhood DNAm can classify prenatal smoke exposure status. Using the Infinium 450 K array, we measured methylation at 26 CpG loci that were previously associated with prenatal smoking in infant cord blood from 572 children, aged 3–5, with differing prenatal exposure to cigarette smoke in the Study to Explore Early Development (SEED). Striking concordance was found between the pattern of prenatal smoking associated DNAm among preschool aged children in SEED and those observed at birth in other studies. These DNAm changes appear to be tobacco-specific. Support vector machine classification models and 10-fold cross-validation were applied to show classification accuracy for childhood DNAm at these 26 sites as a biomarker of prenatal smoking exposure. Classification models showed prenatal exposure to smoking can be assigned with 81% accuracy using childhood DNAm patterns at these 26 loci. These findings support the potential for blood-derived DNAm measurements to serve as biomarkers for prenatal exposure.

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review

“…Mice models show alterations in DNA methylation and airway hyperreactivity in response to in utero ETS [72]. Recent human studies have also found smoke-exposure-specific blood DNA methylation changes present in preschool children, which were comparable to those found at birth [73]. DNA methylation changes following in utero tobacco smoke exposure were also found in fetal lung and placental tissue suggesting a fetal origin for chronic diseases in later life [74].…”

In utero exposure to cigarette smoke and effects across generations: A conference of animals on asthma

“…Meyer et al concluded that the changes in IGF‐1 and IGF‐1R expression, growth restriction and alterations in DNA methylation can lead to higher asthma susceptibility later in life due to the involvement of the IGF axis in lung development. This is of interest as epidemiology studies show that alterations in DNA methylation are associated with increased asthma risk later in life . The abovementioned study was recently confirmed by Dehmel and co‐authors.…”

The Role of Mnk-1, Eukaryotic Translation Initiation Factors and Translation Control in the Pathogenesis of Asthma

“…A second study supported the effect of tobacco smoke during pregnancy on DNA methylation in 572 children. Smoking of mothers during pregnancy reveal increase DNA methylation of the children at school age and the analysis of 26 CpG loci indicated a gene specific methylation pattern including the AHRR and CYP, which are both related to inflammation innate immunity and DNA accessibility [82]. Most of the other loci which were methylated by prenatal smoking have no known function, therefore, their impact on lung function and development has to be further investigated.…”

“…Three recent publications reported that prenatal smoking of mothers induces DNA methylation which seems to be irreversible during the life time of the child [80][81][82]. Comparing the effect of cigarette smoking of mothers during pregnancy in 65 children with asthma to that of 462 children also with asthma born to mothers who did not smoke during pregnancy, significant CpG methylation was observed in 2 genes (FRMD4A, Cllorf52) and a lower increase of methylation in 4 additional genes (XPNPEP1, PPEF2, SMPD3, CRYGN) [81].…”