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环境化学暴露与人类表观遗传学。

Environmental chemical exposures and human epigenetics.

机构信息

Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

出版信息

Int J Epidemiol. 2012 Feb;41(1):79-105. doi: 10.1093/ije/dyr154. Epub 2011 Dec 13.

Abstract

Every year more than 13 million deaths worldwide are due to environmental pollutants, and approximately 24% of diseases are caused by environmental exposures that might be averted through preventive measures. Rapidly growing evidence has linked environmental pollutants with epigenetic variations, including changes in DNA methylation, histone modifications and microRNAs. Environ mental chemicals and epigenetic changes All of these mechanisms are likely to play important roles in disease aetiology, and their modifications due to environmental pollutants might provide further understanding of disease aetiology, as well as biomarkers reflecting exposures to environmental pollutants and/or predicting the risk of future disease. We summarize the findings on epigenetic alterations related to environmental chemical exposures, and propose mechanisms of action by means of which the exposures may cause such epigenetic changes. We discuss opportunities, challenges and future directions for future epidemiology research in environmental epigenomics. Future investigations are needed to solve methodological and practical challenges, including uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to high-throughput epigenomics. In addition, there are numerous reports of epigenetic modifications arising following exposure to environmental toxicants, but most have not been directly linked to disease endpoints. To complete our discussion, we also briefly summarize the diseases that have been linked to environmental chemicals-related epigenetic changes.

摘要

每年,全球有超过 1300 万人的死亡归因于环境污染物,而大约 24%的疾病是由环境暴露引起的,这些暴露本可以通过预防措施避免。越来越多的证据表明,环境污染物与表观遗传变化有关,包括 DNA 甲基化、组蛋白修饰和 microRNAs 的变化。

环境化学物质与表观遗传变化

所有这些机制都可能在疾病发病机制中发挥重要作用,由于环境污染物而发生的改变可能进一步了解疾病发病机制,以及反映环境污染物暴露和/或预测未来疾病风险的生物标志物。我们总结了与环境化学物质暴露相关的表观遗传改变的发现,并提出了作用机制,通过这些机制,暴露可能导致这种表观遗传变化。我们讨论了环境表观基因组学中未来流行病学研究的机会、挑战和未来方向。需要进行未来的调查来解决方法学和实际挑战,包括环境诱导的表观遗传变化随时间的稳定性、表观遗传改变的组织特异性、实验室方法的验证以及生物信息学和生物统计学方法适应高通量表观基因组学等方面的不确定性。此外,有许多关于接触环境毒物后出现表观遗传修饰的报道,但大多数尚未直接与疾病终点联系起来。为了完成我们的讨论,我们还简要总结了与环境化学物质相关的表观遗传变化有关的疾病。

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