Environmental epigenetics and its implication on disease risk and health outcomes

Abstract

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.

Keywords: 5’-hydroxylmethylcytosine; developmental basis of disease; environmental epigenetics; epigenetic memories; exposome; histone modification; low-dose effects; susceptible windows; ten-eleven translocations.

Figure 1

Every individual starts with a defined genetics, which may predispose an individual to certain diseases. During the life course, every individual is exposed to multiple divergent external environment factors (tree) and internal environment factors (lifestyle; flags), leading to different health issues. Depending on the exposures, the magnitude of the epigenomic signature within each individual will differ, leading to changes in the transcriptome. Although some individuals may not advance to the next life stage because of the deadly exposure (dead end), most of them will finish the life journey with differing burden of diseases, depending upon the environment–epigenome interactions that evolve during the life course (e.g., twins will have dissimilar exposures and disease outcomes). The “exposome” is the summation of all exposures an individual experiences over his or her lifetime.