Wittkopp Sharine, Staimer Norbert, Tjoa Thomas, Stinchcombe Timothy, Daher Nancy, Schauer James J, Shafer Martin M, Sioutas Constantinos, Gillen Daniel L, Delfino Ralph J
Occupational and Environmental Medicine Division, Department of Medicine, School of Medicine, University of California, Irvine (UCI), Irvine, California, USA.
Department of Epidemiology, School of Medicine, UCI, Irvine, California, USA.
J Expo Sci Environ Epidemiol. 2016 Mar-Apr;26(2):141-9. doi: 10.1038/jes.2014.84. Epub 2015 Jan 7.
Gene expression changes are linked to air pollutant exposures in in vitro and animal experiments. However, limited data are available on how these outcomes relate to ambient air pollutant exposures in humans. We performed an exploratory analysis testing whether gene expression levels were associated with air pollution exposures in a Los Angeles area cohort of elderly subjects with coronary artery disease. Candidate genes (35) were selected from published studies of gene expression-pollutant associations. Expression levels were measured weekly in 43 subjects (≤ 12 weeks) using quantitative PCR. Exposures included gaseous pollutants O3, nitrogen oxides (NOx), and CO; particulate matter (PM) pollutants elemental and black carbon (EC, BC); and size-fractionated PM mass. We measured organic compounds from PM filter extracts, including polycyclic aromatic hydrocarbons (PAHs), and determined the in vitro oxidative potential of particle extracts. Associations between exposures and gene expression levels were analyzed using mixed-effects regression models. We found positive associations of traffic-related pollutants (EC, BC, primary organic carbon, PM 0.25-2.5 PAH and/or PM 0.25 PAH, and NOx) with NFE2L2, Nrf2-mediated genes (HMOX1, NQO1, and SOD2), CYP1B1, IL1B, and SELP. Findings suggest that NFE2L2 gene expression links associations of traffic-related air pollution with phase I and II enzyme genes at the promoter transcription level.
在体外和动物实验中，基因表达变化与空气污染物暴露有关。然而，关于这些结果与人类环境空气污染物暴露之间的关系，现有数据有限。我们进行了一项探索性分析，以测试在洛杉矶地区患有冠状动脉疾病的老年受试者队列中，基因表达水平是否与空气污染暴露相关。从已发表的基因表达与污染物关联研究中选择了35个候选基因。使用定量PCR每周对43名受试者（≤12周）的基因表达水平进行测量。暴露因素包括气态污染物臭氧（O3）、氮氧化物（NOx）和一氧化碳（CO）；颗粒物（PM）污染物元素碳和黑碳（EC、BC）；以及按粒径分级的PM质量。我们测量了PM过滤器提取物中的有机化合物，包括多环芳烃（PAH），并测定了颗粒提取物的体外氧化潜力。使用混合效应回归模型分析暴露与基因表达水平之间的关联。我们发现交通相关污染物（EC、BC、一次有机碳、PM₂.₅粒径范围内的PAH和/或PM₀.₂₅粒径范围内的PAH以及NOx）与NFE2L2、Nrf2介导的基因（HMOX1、NQO1和SOD2）、CYP1B1、IL1B和SELP呈正相关。研究结果表明，NFE2L2基因表达在启动子转录水平上连接了交通相关空气污染与I相和II相酶基因的关联。
