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Title: Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure
Author: Gruzieva, Olena
Xu, Cheng-Jian
Breton, Carrie V.
Annesi-Maesano, Isabella
Antó i Boqué, Josep Maria
Auffray, Charles
Ballereau, Stephane
Bellander, Tom
Bousquet, Jean
Bustamante Pineda, Mariona
Charles, Marie-Aline
Kluizenaar, Yvonne de
Dekker, Herman T. den
Duijts, Liesbeth
Felix, Janine F.
Gehring, Ulrike
Guxens, Mònica
Jaddoe, Vincent W.
Jankipersadsing, Soesma A.
Merid, Simon Kebede
Kere, Juha
Kumar, Ashish
Lemonnier, Nathanael
Lepeule, Johanna
Nystad, Wenche
Page, Christian Magnus
Panasevich, Sviatlana
Postma, Dirkje S.
Slama, Rémy
Sunyer Deu, Jordi
Soderhall, Cilla
Yao, Jin
London, Stephanie J.
Pershagen, Göran
Koppelman, Gerard H.
Melén, Erik
Keywords: Contaminació
Medicina prenatal
Prenatal medicine
Issue Date: 22-Jul-2016
Publisher: National Institute of Environmental Health Sciences
Abstract: BACKGROUND: Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation. OBJECTIVES: We investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation. METHODS: We meta-analyzed the associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North-American studies (n=1,508) with subsequent look-up analyses in children aged 4 (n=733) and 8 (n=786) years. Additionally, we applied a literature-based candidate approach for antioxidant and anti-inflammatory genes. To assess influence of exposure at the transcriptomics level, we related mRNA expression in blood cells to NO2 exposure in 4- (n=111) and 16-year-olds (n=239). RESULTS: We found epigenome-wide significant associations (false discovery rate (FDR) p<0.05) between maternal NO2 exposure during pregnancy and DNA methylation in newborns for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p<0.05). NO2 exposure at the time of biosampling in childhood had significant impact on CAT and TPO expression. CONCLUSIONS: NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defense pathways.
Note: Versió postprint del document publicat a:
It is part of: Environmental Health Perspectives, 2016
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ISSN: 0091-6765
Appears in Collections:Articles publicats en revistes (ISGlobal)

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