Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic.
Department of Nanotoxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic.
Int J Mol Sci. 2022 Jan 31;23(3):1666. doi: 10.3390/ijms23031666.
DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and it can serve as a useful biomarker of prior environmental exposure and future health outcomes. This study focused on DNA methylation profiles in a human cohort, comprising 125 nonsmoking city policemen (sampled twice), living and working in three localities (Prague, Ostrava and Ceske Budejovice) of the Czech Republic, who spent the majority of their working time outdoors. The main characterization of the localities, differing by major sources of air pollution, was defined by the stationary air pollution monitoring of PM2.5, B[a]P and NO. DNA methylation was analyzed by a genome-wide microarray method. No season-specific DNA methylation pattern was discovered; however, we identified 13,643 differentially methylated CpG loci (DML) for a comparison between the Prague and Ostrava groups. The most significant DML was cg10123377 (logFC = -1.92, = 8.30 × 10) and loci annotated to (total 20 CpG loci). We also found two hypomethylated loci annotated to the DNA repair gene Groups of DML annotated to the same gene were linked to diabetes mellitus (), respiratory diseases (), the dopaminergic system of the brain and neurodegenerative diseases (). The most significant possibly affected pathway was Axon guidance, with 86 potentially deregulated genes near DML. The cluster of gene sets that could be affected by DNA methylation in the Ostrava groups mainly includes the neuronal functions and biological processes of cell junctions and adhesion assembly. The study demonstrates that the differences in the type of air pollution between localities can affect a unique change in DNA methylation profiles across the human genome.
DNA 甲基化是研究最为广泛的表观遗传机制之一，可作为先前环境暴露和未来健康结果的有用生物标志物。本研究关注人类队列中的 DNA 甲基化谱，该队列由 125 名不吸烟的城市警察组成（两次采样），他们居住和工作在捷克共和国的三个地方（布拉格、俄斯特拉发和布尔诺），大部分工作时间都在户外。这些地方的主要特征是通过对 PM2.5、B[a]P 和 NO 的固定空气污染物监测来定义的。通过全基因组微阵列方法分析 DNA 甲基化。未发现具有特定季节性的 DNA 甲基化模式；然而，我们在布拉格和俄斯特拉发组之间的比较中鉴定出了 13643 个差异甲基化 CpG 位点（DML）。最显著的 DML 是 cg10123377（logFC = -1.92， = 8.30 × 10），并注释到 （总共 20 个 CpG 位点）。我们还发现两个位于 DNA 修复基因 的低甲基化位点。注释到同一基因的 DML 组与糖尿病（）、呼吸疾病（）、大脑多巴胺能系统和神经退行性疾病（）相关。最显著的可能受影响途径是轴突导向，在 DML 附近有 86 个可能失调的基因。受 Ostrava 组 DNA 甲基化影响的基因集簇主要包括神经元功能和细胞连接和粘附组装的生物学过程。该研究表明，地方之间的空气污染类型的差异可能会影响整个人类基因组中 DNA 甲基化谱的独特变化。
