Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure.
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Gruzieva Olena, Xu Cheng-Jian, Breton Carrie V, Annesi-Maesano Isabella, Antó Josep M, Auffray Charles, Ballereau Stéphane, Bellander Tom, Bousquet Jean, Bustamante Mariona, Charles Marie-Aline, de Kluizenaar Yvonne, den Dekker Herman T, Duijts Liesbeth, Felix Janine F, Gehring Ulrike, Guxens Mònica, Jaddoe Vincent V W, Jankipersadsing Soesma A, Merid Simon Kebede, Kere Juha, Kumar Ashish, Lemonnier Nathanael, Lepeule Johanna, Nystad Wenche, Page Christian Magnus, Panasevich Sviatlana, Postma Dirkje, Slama Rémy, Sunyer Jordi, Söderhäll Cilla, Yao Jin, London Stephanie J, Pershagen Göran, Koppelman Gerard H, Melén Erik
Аннотация
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 ages 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 a 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. Citation: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. 2017. Epigenome-wide meta-analysis of methylation in children related to prenatal NO2 air pollution exposure. Environ Health Perspect 125:104-110; http://dx.doi.org/10.1289/EHP36.