Dataset Information

Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study.

ABSTRACT: MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects. In addition to human miRNAs, viral miRNAs expressed from latent viral sequences are detectable in human cells.In a highly exposed population in Beijing, China, we evaluated the associations of particulate air pollution exposure on blood miRNA profiles.The Beijing Truck Driver Air Pollution Study (BTDAS) included 60 truck drivers and 60 office workers. We investigated associations of short-term air pollution exposure, using measures of personal PM2.5 (particulate matter ? 2.5 ?m) and elemental carbon (EC), and ambient PM10 (? 10 ?m), with blood NanoString nCounter miRNA profiles at two exams separated by 1-2 weeks.No miRNA was significantly associated with personal PM2.5 at a false discovery rate (FDR) of 20%. Short-term ambient PM10 was associated with the expression of 12 miRNAs in office workers only (FDR < 20%). Short-term EC was associated with differential expression of 46 human and 7 viral miRNAs, the latter including 3 and 4 viral miRNAs in office workers and truck drivers, respectively. EC-associated miRNAs differed between office workers and truck drivers with significant effect modification by occupational group. Functional interaction network analysis suggested enriched cellular proliferation/differentiation pathways in truck drivers and proinflammation pathways in office workers.Short-term EC exposure was associated with the expression of human and viral miRNAs that may influence immune responses and other biological pathways. Associations between EC exposure and viral miRNA expression suggest that latent viral miRNAs are potential mediators of air pollution-associated health effects. PM2.5/PM10 exposures showed no consistent relationships with miRNA expression.

SUBMITTER: Hou L

PROVIDER: S-EPMC4786978 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study.

Hou Lifang L Barupal Jitendra J Zhang Wei W Zheng Yinan Y Liu Lei L Zhang Xiao X Dou Chang C McCracken John P JP Díaz Anaité A Motta Valeria V Sanchez-Guerra Marco M Wolf Katherine Rose KR Bertazzi Pier Alberto PA Schwartz Joel D JD Wang Sheng S Baccarelli Andrea A AA

Environmental health perspectives 20150612 3

<h4>Background</h4>MicroRNAs (miRNAs) are post-transcriptional gene suppressors and potential mediators of environmental effects. In addition to human miRNAs, viral miRNAs expressed from latent viral sequences are detectable in human cells.<h4>Objective</h4>In a highly exposed population in Beijing, China, we evaluated the associations of particulate air pollution exposure on blood miRNA profiles.<h4>Methods</h4>The Beijing Truck Driver Air Pollution Study (BTDAS) included 60 truck drivers and 6 ...[more]

PMID: 26068961

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Project description:BackgroundPost-transcriptional modifications of RNA constitute fundamental mechanisms of gene regulation. N6-methyladenosine (m6A) is critical for health and disease and is modulated by cellular stressors. However, associations between environmental exposures and m6A have not been studied in humans. We aimed to examine associations between tobacco smoking and particulate air pollution with m6A and mRNA expression levels of its reader, writer and eraser (RWE) genes in blood.MethodsUsing the Beijing Truck Driver Air Pollution Study, we investigated global m6A in RNA from peripheral blood collected from 106 human subjects in Beijing, China, in 2008. We measured m6A with nano-flow liquid chromatography-tandem mass spectrometry and investigated gene expression of six m6A RWEs with real-time-quantitative PCR. Using linear models, we examined associations with smoking status, pack-years, and smoking on day of visit in men, and with environmental tobacco smoke in nonsmokers. We also examined associations with ambient PM10 (particulate matter ≤ 10 µm in diameter), and personal black carbon (BC) and PM2.5 measured with a portable monitor.ResultsSmoking in men was significantly associated with a relative 10.7% decrease in global m6A levels in comparison to nonsmokers (p = 0.02). In men, smoking greater than 3.8 pack-years was associated with a 14.9% lower m6A than in nonsmokers. BC exposure trended towards positive associations with m6A (5.95% per 10 μg/m3 increase in BC; 95% CI: -0.96, 13.3). Global m6A levels were not correlated with RWE gene expression levels. No associations were detected between smoking or air pollutants and m6A RWE gene expression.Discussionm6A was negatively associated with long-term smoking, yet positively associated with short-term BC exposure. These results indicate variable m6A responses to environmental stressors, providing early evidence into the impacts of toxicants on RNA modifications and suggesting potential for m6A as a biomarker or mechanism in environmental health research.

Project description:Ambient particulate matter (PM) has been associated with mortality and morbidity for cardiovascular disease. MicroRNAs control gene expression at a posttranscriptional level. Altered microRNA expression has been reported in processes related to cardiovascular disease and PM exposure, such as systemic inflammation, endothelial dysfunction, and atherosclerosis. Polymorphisms in microRNA-related genes could influence response to PM.We investigated the association of exposure to ambient particles in several time windows (4-hour to 28-day moving averages) and blood leukocyte expression changes in 14 candidate microRNAs in 153 elderly males from the Normative Aging Study (examined 2005-2009). Potential effect modification by six single nucleotide polymorphisms (SNPs) in three microRNA-related genes was investigated. Fine PM (PM2.5), black carbon, organic carbon, and sulfates were measured at a stationary ambient monitoring site. Linear regression models, adjusted for potential confounders, were used to assess effects of particles and SNP-by-pollutant interaction. An in silico pathway analysis was performed on target genes of microRNAs associated with the pollutants.We found a negative association for pollutants in all moving averages and miR-1, -126, -135a, -146a, -155, -21, -222, and -9. The strongest associations were observed with the 7-day moving averages for PM2.5 and black carbon and with the 48-hour moving averages for organic carbon. The association with sulfates was stable across the moving averages. The in silico pathway analysis identified 18 pathways related to immune response shared by at least two microRNAs; in particular, the "high-mobility group protein B1/advanced glycosylation end product-specific receptor signaling pathway" was shared by miR-126, -146a, -155, -21, and -222. No important associations were observed for miR-125a-5p, -125b, -128, -147, -218, and -96. We found significant SNP-by-pollutant interactions for rs7813, rs910925, and rs1062923 in GEMIN4 and black carbon and PM2.5 for miR-1, -126, -146a, -222, and -9, and for rs1640299 in DGCR8 and SO4 for miR-1 and -135a.Exposure to ambient particles could cause a downregulation of microRNAs involved in processes related to PM exposure. Polymorphisms in GEMIN4 and DGCR8 could modify these associations.

Dataset Information

Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study.

Publications

Particulate Air Pollution Exposure and Expression of Viral and Human MicroRNAs in Blood: The Beijing Truck Driver Air Pollution Study.

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