Autor/a:
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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
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Abstract:
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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. |