Ho Shuk-Mei, Johnson Abby, Tarapore Pheruza, Janakiram Vinothini, Zhang Xiang, Leung Yuet-Kin
Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
ILAR J. 2012;53(3-4):289-305. doi: 10.1093/ilar.53.3-4.289.
This review focuses on how environmental factors through epigenetics modify disease risk and health outcomes. Major epigenetic events, such as histone modifications, DNA methylation, and microRNA expression, are described. The function of dose, duration, composition, and window of exposure in remodeling the individual's epigenetic terrain and disease susceptibility are addressed. The ideas of lifelong editing of early-life epigenetic memories, transgenerational effects through germline transmission, and the potential role of hydroxylmethylation of cytosine in developmental reprogramming are discussed. Finally, the epigenetic effects of several major classes of environmental factors are reviewed in the context of pathogenesis of disease. These include endocrine disruptors, tobacco smoke, polycyclic aromatic hydrocarbons, infectious pathogens, particulate matter, diesel exhaust particles, dust mites, fungi, heavy metals, and other indoor and outdoor pollutants. We conclude that the summation of epigenetic modifications induced by multiple environmental exposures, accumulated over time, represented as broad or narrow, acute or chronic, developmental or lifelong, may provide a more precise assessment of risk and consequences. Future investigations may focus on their use as readouts or biomarkers of the totality of past exposure for the prediction of future disease risk and the prescription of effective countermeasures.
本综述聚焦于环境因素如何通过表观遗传学改变疾病风险和健康结局。文中描述了主要的表观遗传事件,如组蛋白修饰、DNA甲基化和微小RNA表达。探讨了剂量、持续时间、成分和暴露窗口期在重塑个体表观遗传格局及疾病易感性方面的作用。讨论了对早期表观遗传记忆进行终身编辑的观点、通过种系传递产生的跨代效应以及胞嘧啶羟甲基化在发育重编程中的潜在作用。最后,在疾病发病机制的背景下综述了几大类环境因素的表观遗传效应。这些因素包括内分泌干扰物、烟草烟雾、多环芳烃、传染性病原体、颗粒物、柴油尾气颗粒、尘螨、真菌、重金属以及其他室内外污染物。我们得出结论,随着时间积累,由多种环境暴露诱导的表观遗传修饰总和,无论其表现为广泛或局限、急性或慢性、发育阶段或终身影响,都可能为风险和后果提供更精确的评估。未来的研究可能会聚焦于将这些修饰用作过去暴露总量的读数或生物标志物,以预测未来疾病风险并制定有效的应对措施。