标题：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
期刊名称：Environmental Health - a Global Access Science Source
印刷版ISSN：1476-069X
电子版ISSN：1476-069X
出版年度：2014
卷号：13
期号：1
页码：94
DOI：10.1186/1476-069X-13-94
语种：English
出版社：BioMed Central
摘要：Exposure 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. We 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. Specifically, 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. Exposure 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.
关键词：Black Carbon ; Cigarette Smoke Extract ; Exposure Model ; MAPK Gene ; Normative Aging Study
