Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	DNA methylation and exposure to ambient air pollution in two prospective cohorts
Δημιουργός/Συγγραφέας:	Plusquin M. Guida F. Polidoro S. Vermeulen R. Raaschou-Nielsen O. Campanella G. Hoek G. [EL] Κυρτόπουλος, Σωτήριος Α.[EN] Kyrtopoulos, Soterios A. [EL] Γεωργιάδης, Παναγιώτης[EN] Georgiadis, Panagiotis Naccarati A. Sacerdote C. Krogh V. Bas Bueno-de-Mesquita H. Monique Verschuren W.M. Sayols-Baixeras S. Panni T. Peters A. Hebels D.G.A.J. Kleinjans J. Vineis P. Chadeau-Hyam M.
Εκδότης:	Elsevier Ltd
Ημερομηνία:	2017
Γλώσσα:	Αγγλικά
ISSN:	0160-4120
DOI:	10.1016/j.envint.2017.08.006
Άλλο:	PubMed ID: 28843141
Περίληψη:	Long-term exposure to air pollution has been associated with several adverse health effects including cardiovascular, respiratory diseases and cancers. However, underlying molecular alterations remain to be further investigated. The aim of this study is to investigate the effects of long-term exposure to air pollutants on (a) average DNA methylation at functional regions and, (b) individual differentially methylated CpG sites. An assumption is that omic measurements, including the methylome, are more sensitive to low doses than hard health outcomes. This study included blood-derived DNA methylation (Illumina-HM450 methylation) for 454 Italian and 159 Dutch participants from the European Prospective Investigation into Cancer and Nutrition (EPIC). Long-term air pollution exposure levels, including NO2, NOx, PM2.5, PMcoarse, PM10, PM2.5 absorbance (soot) were estimated using models developed within the ESCAPE project, and back-extrapolated to the time of sampling when possible. We meta-analysed the associations between the air pollutants and global DNA methylation, methylation in functional regions and epigenome-wide methylation. CpG sites found differentially methylated with air pollution were further investigated for functional interpretation in an independent population (EnviroGenoMarkers project), where (N = 613) participants had both methylation and gene expression data available. Exposure to NO2 was associated with a significant global somatic hypomethylation (p-value = 0.014). Hypomethylation of CpG island's shores and shelves and gene bodies was significantly associated with higher exposures to NO2 and NOx. Meta-analysing the epigenome-wide findings of the 2 cohorts did not show genome-wide significant associations at single CpG site level. However, several significant CpG were found if the analyses were separated by countries. By regressing gene expression levels against methylation levels of the exposure-related CpG sites, we identified several significant CpG-transcript pairs and highlighted 5 enriched pathways for NO2 and 9 for NOx mainly related to the immune system and its regulation. Our findings support results on global hypomethylation associated with air pollution, and suggest that the shores and shelves of CpG islands and gene bodies are mostly affected by higher exposure to NO2 and NOx. Functional differences in the immune system were suggested by transcriptome analyses.
Τίτλος πηγής δημοσίευσης:	Environment International
Τόμος/Κεφάλαιο:	108
Σελίδες:	127-136
Θεματική Κατηγορία:	[EL] Τοξικολογία[EN] Toxicology. Poisons
Λέξεις-Κλειδιά:	Air pollution EPIC Epigenome-wide DNA methylation Illumina 450 k human methylation array NOx Particulate matter
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2017 The Authors
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Hybrid Gold, Green
Σημειώσεις:	Hedge Funds Care; Society of Gastrointestinal Radiologists; Compagnia di San Paolo; NERC Environmental Bioinformatics Centre; Netherlands Leprosy Relief; Seventh Framework Programme: 628858; Institute of Infection and Immunity; Medical Research Council: MR/L01341X/1; Cancer Research UK: 22184; World Cancer Research Fund; Marie Curie Cancer Care; Imperial College London: HERACLES RD12/0042, PI09/90506, PI12/00232, RD12/0042, SGR 1195; European Commission; Research Executive Agency; Colt Foundation; ZonMw; Public Health England; Innovation and Technology Commission; Ministry of Health, Labour and Welfare; Human Genetics Foundation-Torino; Instituto de Salud Carlos III: IFI14/00007; Associazione Italiana per la Ricerca sul Cancro; Ministry of Economy; European Regional Development Fund; Instituto Carlos Slim de la Salud.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο