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| Status |
Public on Feb 16, 2015 |
| Title |
DNA methylation patterns in newborns exposed to tobacco in utero |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
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 (for methylation arrays) and maternal peripheral venous blood (for cotine level measurement) were collected and an epigenome-wide association study was performed using a 450K 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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| Overall design |
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 were collected and an epigenome-wide association study was performed using a 450K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.
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| Contributor(s) |
Ivorra C, Fraga MF, Bayón GF, Fernández AF, García-Vicent C, Chaves FJ, Redon J, Lurbe E |
| Citation(s) |
25623364 |
| Submission date |
Dec 18, 2014 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Agustin F Fernandez |
| E-mail(s) |
affernandez@hca.es, agusff@gmail.com
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| Phone |
985652411
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| Organization name |
Oviedo University-HUCA
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| Department |
IUOPA
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| Lab |
Epigenetics
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| Street address |
Avenida de Roma s/n
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| City |
Oviedo |
| State/province |
Asturias |
| ZIP/Postal code |
33011 |
| Country |
Spain |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA270729 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE64316_RAW.tar |
183.1 Mb |
(http)(custom) |
TAR |
| GSE64316_non_normalized.txt.gz |
62.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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