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|Title: ||DNA methylation and exposure to ambient air pollution in two prospective cohorts|
|Authors: ||Plusquin, Michelle|
Kyrtopoulos, Soterios A.
Bueno-de-Mesquita, H. Bas
Verschuren, W. M. Monique
Hebels, Dennie G. A. J.
|Issue Date: ||2017|
|Publisher: ||PERGAMON-ELSEVIER SCIENCE LTD|
|Citation: ||ENVIRONMENT INTERNATIONAL, 108, p. 127-136|
|Abstract: ||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.|
|Notes: ||[Plusquin, Michelle; Guida, Florence; Campanella, Gianluca; Bueno-de-Mesquita, H. Bas; Vineis, Paolo; Chadeau-Hyam, Marc] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Plusquin, Michelle; Guida, Florence; Vermeulen, Roel; Campanella, Gianluca; Vineis, Paolo; Chadeau-Hyam, Marc] Imperial Coll London, Med Res Council, Hlth Protect Agcy, Ctr Environm & Hlth, London, England. [Plusquin, Michelle] Hasselt Univ, Ctr Environm Sci, Hasselt, Belgium. [Polidoro, Silvia; Naccarati, Alessio; Vineis, Paolo] IIGM, Turin, Italy. [Vermeulen, Roel; Hoek, Gerard; Chadeau-Hyam, Marc] Univ Utrecht, Div Environm Epidemiol, IRAS, Utrecht, Netherlands. [Raaschou-Nielsen, Ole] Danish Canc Soc, Res Ctr, Copenhagen, Denmark. [Raaschou-Nielsen, Ole] Aarhus Univ, Dept Environm Sci, Roskilde, Denmark. [Kyrtopoulos, Soterios A.; Georgiadis, Panagiotis] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, 48 Vas Constantinou Ave, Athens 11635, Greece. [Sacerdote, Carlotta] Univ Turin, Dept Med Sci, Unit Canc Epidemiol CERMS, Turin, Italy. [Sacerdote, Carlotta] Citta Salute & Sci Hosp, Turin, Italy. [Krogh, Vittorio] Ist Nazl Tumori, Fdn IRCCS, Dept Prevent & Predict Med, Epidemiol Unit, Milan, Italy. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia. [Verschuren, W. M. Monique] UMC Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Verschuren, W. M. Monique] Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands. [Sayols-Baixeras, Sergi] Hosp del Mar, Med Res Inst, IMIM, Cardiovasc Epidemiol & Genet Res Grp, Barcelona 08003, Catalonia, Spain. [Sayols-Baixeras, Sergi] UPF, Barcelona 08003, Catalonia, Spain. [Panni, Tommaso; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Hebels, Dennie G. A. J.; Kleinjans, Jos] Maastricht Univ, Dept Toxicogen, Maastricht, Netherlands. [Hebels, Dennie G. A. J.] Maastricht Univ, MERLN Inst, Dept Cell Biol Inspired Tissue Engn, Maastricht, Netherlands.|
|ISI #: ||000411604400013|
|Type: ||Journal Contribution|
|Validation: ||ecoom, 2018|
|Appears in Collections: ||Research publications|
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