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. 2015 Jan 27:13:25.
doi: 10.1186/s12967-015-0384-5.

DNA methylation patterns in newborns exposed to tobacco in utero

Carmen Ivorra  1   2 , Mario F Fraga  3 , Gustavo F Bayón  4 , Agustín F Fernández  5 , Consuelo Garcia-Vicent  6 , F Javier Chaves  7   8 , Josep Redon  9   10 , Empar Lurbe  11   12
Affiliations

DNA methylation patterns in newborns exposed to tobacco in utero

Carmen Ivorra et al. J Transl Med. .

Abstract

Background: Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.

Methods: Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood and maternal peripheral venous blood were collected and an epigenome-wide association study was performed using a 450 K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.

Results: The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (Fisher's exact test, p = 0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene.

Conclusions: In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease.

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Figures

Figure 1
Figure 1
Global DNA Methylation. A) Global DNA methylation index in cord blood DNA of 10 newborns exposed to in utero tobacco, and 10 newborns non-exposed to in utero tobacco (Box plots). B) Manhattan plot for methylation status in umbilical cord blood DNA from newborns exposed or non-exposed to in utero tobacco. The vertical axis indicates (-log10 transformed) observed p-values and the horizontal threshold indicates the significance level (p = 1x10−5).
Figure 2
Figure 2
Location of the 31 CpG sites differentially methylated compared to all CpGs on the methylation array (all probes). Methylation sites were categorized in groups according to their location.
Figure 3
Figure 3
Hierarchical clustering heat map including the CpG sites with significant differential methylation between exposed and non-exposed newborns.
See this image and copyright information in PMC

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References

    1. Brion MJ, Leary SD, Lawlor DA, Smith GD, Ness AR. Modifiable maternal exposures and offspring blood pressure: a review of epidemiological studies of maternal age, diet, and smoking. Pediatr Res. 2008;63:593–8. doi: 10.1203/PDR.0b013e31816fdbd3. - DOI - PubMed
    1. Cupul-Uicab LA, Skjaerven R, Haug K, Melve KK, Engel SM, Longnecker MP. In utero exposure to maternal tobacco smoke and subsequent obesity, hypertension, and gestational diabetes among women in the MoBa cohort. Environ Health Perspect. 2012;120:355–60. doi: 10.1289/ehp.1103789. - DOI - PMC - PubMed
    1. von Kries R, Bolte G, Baghi L, Toschke AM, GME Study Group Parental smoking and childhood obesity–is maternal smoking in pregnancy the critical exposure? Int J Epidemiol. 2008;37:210–6. doi: 10.1093/ije/dym239. - DOI - PubMed
    1. Puig C, Vall O, García-Algar O, Papaseit E, Pichini S, Saltó E, et al. Assessment of prenatal exposure to tobacco smoke by cotinine in cord blood for the evaluation of smoking control policies in Spain. BMC Pregnancy Childbirth. 2012;12:26. doi: 10.1186/1471-2393-12-26. - DOI - PMC - PubMed
    1. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447:425–32. doi: 10.1038/nature05918. - DOI - PubMed

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