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儿童接触空气污染与基因表达有关。

Air pollution exposure is associated with gene expression in children.

作者信息

Das Siddhartha, Rundblad Amanda, Marques Irene Fontes, Soares Ana Goncalves, Jaddoe Vincent W, Vrijheid Martine, Nieuwenhuijsen Mark, Verlouw Joost, Matthews Jason, Holven Kirsten B, Thoresen Magne, Timpson Nicholas J, Felix Janine F, Ulven Stine M

机构信息

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo 0317, Norway.

Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 GD, the Netherlands.

出版信息

Environ Epigenet. 2024 Dec 21;10(1):dvae025. doi: 10.1093/eep/dvae025. eCollection 2024.

Abstract

Environmental exposures, including air pollutants and lack of natural spaces, are associated with suboptimal health outcomes in children. We aimed to study the associations between environmental exposures and gene expression in children. Associations of exposure to particulate matter (PM) with diameter <2.5 (PM) and < 10 (PM) micrometers, nitrogen dioxide, green spaces, and blue space, with whole-blood gene expression were explored in children from the Dutch Generation R Study ( = 172). Analyses were adjusted for age, sex, batch, maternal education, and area socioeconomic status. Follow-up analysis was carried out using lymphoblastoid cell line gene expression in children from the ALSPAC Study ( = 946). Gene set enrichment analysis (GSEA) using hallmark and immune gene sets from the molecular signature database was carried out to identify significantly over-represented gene sets for insights into biological mechanisms Exposure to PM was associated with expression of 86 genes in discovery analyses in the Generation R Study [false discovery rate (FDR)-adjusted -value < .25]. Of these, PM was also associated with expression in the same direction in follow-up analysis (FDR-adjusted -value < .05). The remaining exposures showed much fewer associations in the discovery analyses. GSEA using PM association results for both cohorts indicated suppression of gene sets related to interferon response and response to bacterial and viral exposure. In conclusion, gene expression analysis performed in two independent cohorts suggests that PM exposure in children may be involved in interferon and microbial infection responses.

摘要

环境暴露,包括空气污染物和缺乏自然空间,与儿童健康状况不佳有关。我们旨在研究环境暴露与儿童基因表达之间的关联。在荷兰Generation R研究中的儿童(n = 172)中,探讨了暴露于直径<2.5微米(PM2.5)和<10微米(PM10)的颗粒物、二氧化氮、绿地和蓝色空间与全血基因表达之间的关联。分析针对年龄、性别、批次、母亲教育程度和地区社会经济地位进行了调整。使用阿冯纵向父母与儿童发育研究(ALSPAC)中的儿童(n = 946)的淋巴母细胞系基因表达进行了随访分析。使用来自分子特征数据库的标志性和免疫基因集进行基因集富集分析(GSEA),以识别显著过度代表的基因集,从而深入了解生物学机制。在Generation R研究的发现分析中,暴露于PM与86个基因的表达相关[错误发现率(FDR)调整后的P值<0.25]。其中,在随访分析中,PM也与相同方向的表达相关(FDR调整后的P值<0.05)。在发现分析中,其余暴露显示的关联要少得多。对两个队列使用PM关联结果进行的GSEA表明,与干扰素反应以及对细菌和病毒暴露的反应相关的基因集受到抑制。总之,在两个独立队列中进行的基因表达分析表明,儿童暴露于PM可能参与了干扰素和微生物感染反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/909b/11668970/c1e19fac6b0c/dvae025fa1.jpg

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