Zhao Meiduo, Wu Jingtao, Xu Jing, Li Ang, Mei Yayuan, Ge Xiaoyu, Yin Guohuan, Liu Xiaolin, Wei Lanping, Xu Qun
Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Front Genet. 2023 Jan 4;13:1043486. doi: 10.3389/fgene.2022.1043486. eCollection 2022.
Previous studies have reported that chromium (Cr)-induced epigenetic alterations and DNA methylation play a vital role in the pathogenesis of diseases induced by chromium exposure. Epigenomic analyses have been limited and mainly focused on occupational chromium exposure; their findings are not generalizable to populations with environmental Cr exposure. We identified the differential methylation of genes and regions to elucidate the mechanisms of toxicity related to environmental chromium exposure. DNA methylation was measured in blood samples collected from individuals in Cr-contaminated ( = 10) and unexposed areas ( = 10) by using the Illumina Infinium HumanMethylation850K array. To evaluate the relationship between chromium levels in urine and CpG methylation at 850 thousand sites, we investigated differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by using linear models and DMRcate method, respectively. The model was adjusted for biologically relevant variables and estimated cell-type compositions. At the epigenome-wide level, we identified five CpGs [cg20690919 ( 0.006), cg00704664 ( 0.024), cg10809143 ( 0.043), cg27057652 ( 0.047), cg05390480 ( 0.024)] and one DMR (chr17: 19,648,718-19,648,972), annotated to genes ( < 0.05) as being significantly associated with log transformed urinary chromium levels. Environmental chromium exposure is associated with DNA methylation, and the significant DMPs and DMR being annotated to cause DNA damage and genomic instability were found in this work. Research involving larger samples is required to further explore the epigenetic effect of environmental chromium exposure on health outcomes through DNA methylation.
先前的研究报道,铬(Cr)诱导的表观遗传改变和DNA甲基化在铬暴露所致疾病的发病机制中起着至关重要的作用。表观基因组分析有限,且主要集中在职业性铬暴露方面;其研究结果不能推广到环境铬暴露人群。我们鉴定了基因和区域的差异甲基化,以阐明与环境铬暴露相关的毒性机制。通过使用Illumina Infinium HumanMethylation850K芯片,对从铬污染地区(n = 10)和未暴露地区(n = 10)的个体采集的血液样本进行DNA甲基化检测。为了评估尿铬水平与85万个位点的CpG甲基化之间的关系,我们分别使用线性模型和DMRcate方法研究了差异甲基化位点(DMPs)和差异甲基化区域(DMRs)。该模型针对生物学相关变量进行了校正,并估计了细胞类型组成。在全表观基因组水平上,我们鉴定出5个CpG位点[cg20690919(p = 0.006)、cg00704664(p = 0.024)、cg10809143(p = 0.043)、cg27057652(p = 0.047)、cg05390480(p = 0.024)]和1个DMR(chr17: 19,648,718 - 19,648,972),注释到基因(p < 0.05),与对数转换后的尿铬水平显著相关。环境铬暴露与DNA甲基化有关,并且在本研究中发现了注释为导致DNA损伤和基因组不稳定的显著DMPs和DMRs。需要开展涉及更大样本量的研究,以通过DNA甲基化进一步探索环境铬暴露对健康结局的表观遗传效应。