Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

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...

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Detalhes bibliográficos
Autores: 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
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2016
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/101564
Acesso em linha:https://hdl.handle.net/2445/101564
Access Level:Acceso aberto
Palavra-chave:Contaminació
Medicina prenatal
Pollution
Prenatal medicine
Descrição
Resumo: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.

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