Gene expression network analyses in response to air pollution exposures in the trucking industry.

Gene expression network analyses in response to air pollution exposures in the trucking industry.
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DOI:
10.1186/s12940-016-0187-z
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发表时间:
2016-11-03
期刊:
Environmental health : a global access science source
影响因子:
--
通讯作者:
Laden F
Laden F
中科院分区:
其他
文献类型:
--
作者:
Chu JH;Hart JE;Chhabra D;Garshick E;Raby BA;Laden F

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暴露于空气污染,包括与交通有关的污染物,与各种不利的健康后果有关,包括心肺发病率和死亡率增加,以及肺癌风险增加。为了更好地了解空气污染暴露引起的细胞反应,我们使用在美国东北部10个卡车码头的63名不吸烟员工工作周的三个时间点采集的全血RNA,进行了全基因组基因表达微阵列分析。我们定义了对PM2.5(直径2.5微米的颗粒物 ≤ )、元素碳(EC)和有机碳(OC)有不同反应的基因和基因网络。多个转录本(PADJ < 0.001)与污染物水平(EC、OC和PM2.5中分别为48、260和49个转录本)密切相关,其中63个转录本与三种暴露中的至少两种在统计学上显著相关。这些基因包括许多与缺血性心脏病、慢性阻塞性肺疾病(COPD)、肺癌和其他污染相关疾病有关的基因。通过结合基因集浓缩分析和网络分析(使用GeneMANIA),我们确定了25个相关基因的核心集合,这些基因在所有三种暴露措施中都是共同的,并且在之前两项评估空气污染基因表达的研究中存在差异表达。其中许多是与癌症相关的基本途径的成员,包括与DNA和金属结合相关的途径,以及细胞凋亡的调节,但也包括与慢性心肺疾病有关的基因。这些数据提供了空气污染暴露与健康影响之间的分子联系。本文的在线版本(doi:10.1186/s12940-0160187-z)包含补充材料,授权用户可以使用。
Exposure to air pollution, including traffic-related pollutants, has been associated with a variety of adverse health outcomes, including increased cardiopulmonary morbidity and mortality, and increased lung cancer risk. To better understand the cellular responses induced by air pollution exposures, we performed genome-wide gene expression microarray analysis using whole blood RNA sampled at three time-points across the work weeks of 63 non-smoking employees at 10 trucking terminals in the northeastern US. We defined genes and gene networks that were differentially activated in response to PM2.5 (particulate matter ≤ 2.5 microns in diameter) and elemental carbon (EC) and organic carbon (OC). Multiple transcripts were strongly associated (padj < 0.001) with pollutant levels (48, 260, and 49 transcripts for EC, OC, and PM2.5, respectively), including 63 that were statistically significantly correlated with at least two out of the three exposures. These genes included many that have been implicated in ischemic heart disease, chronic obstructive pulmonary disease (COPD), lung cancer, and other pollution-related illnesses. Through the combination of Gene Set Enrichment Analysis and network analysis (using GeneMANIA), we identified a core set of 25 interrelated genes that were common to all three exposure measures and were differentially expressed in two previous studies assessing gene expression attributable to air pollution. Many of these are members of fundamental cancer-related pathways, including those related to DNA and metal binding, and regulation of apoptosis and also but include genes implicated in chronic heart and lung diseases. These data provide a molecular link between the associations of air pollution exposures with health effects. The online version of this article (doi:10.1186/s12940-016-0187-z) contains supplementary material, which is available to authorized users.
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