Short-term airborne particulate matter exposure alters the epigenetic landscape of human genes associated with the mitogen-activated protein kinase network: a cross-sectional study

Environmental Health

Research

John Hutchinson¹  Laura Cantone²  Arnab Maity³  Joel Schwartz⁴  Juan Jose Carmona⁵  Andrea A Baccarelli⁵  Brent Coull⁶  Tamar Sofer⁶  Xihong Lin⁶  Pantel Vokonas⁷ 

[1] Center for Health Bioinformatics, Harvard School of Public Health, Boston, MA, USA;Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy;Department of Statistics, North Carolina State University, Raleigh, NC, USA;Laboratory of Human Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Laboratory of Human Environmental Epigenetics, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Exposure, Epidemiology, and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Program in Quantitative Genomics, Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA;Program in Quantitative Genomics, Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA;VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA;

关键词: Black Carbon;    Cigarette Smoke Extract;    Exposure Model;    MAPK Gene;    Normative Aging Study;   

DOI  :  10.1186/1476-069X-13-94

 received in 2014-05-02, accepted in 2014-10-06,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundExposure to air particulate matter is known to elevate blood biomarkers of inflammation and to increase cardiopulmonary morbidity and mortality. Major components of airborne particulate matter typically include black carbon from traffic and sulfates from coal-burning power plants. DNA methylation is thought to be sensitive to these environmental toxins and possibly mediate environmental effects on clinical outcomes via regulation of gene networks. The underlying mechanisms may include epigenetic modulation of major inflammatory pathways, yet the details remain unclear.MethodsWe sought to elucidate how short-term exposure to air pollution components, singly and/or in combination, alter blood DNA methylation in certain inflammation-associated gene networks, MAPK and NF-κB, which may transmit the environmental signal(s) and influence the inflammatory pathway in vivo. To this end, we utilized a custom-integrated workflow—molecular processing, pollution surveillance, biostatical analysis, and bioinformatic visualization—to map novel human (epi)gene pathway-environment interactions.ResultsSpecifically, out of 84 MAPK pathway genes considered, we identified 11 whose DNA methylation status was highly associated with black carbon exposure, after adjusting for potential confounders—age, sulfate exposure, smoking, blood cell composition, and blood pressure. Moreover, after adjusting for these confounders, multi-pollutant analysis of synergistic DNA methylations significantly associated with sulfate and BC exposures yielded 14 MAPK genes. No associations were found with the NF-κB pathway.ConclusionExposure to short-term air pollution components thus resulted in quantifiable epigenetic changes in the promoter areas of MAPK pathway genes. Bioinformatic mapping of single- vs. multi-exposure-associated epigenetic changes suggests that these alterations might affect biological pathways in nuanced ways that are not simply additive or fully predictable via individual-level exposure assessments.

【 授权许可】

Unknown   
© Carmona et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.