Environmental exposures and gene regulation in disease etiology.
OBJECTIVE
Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here.


METHODS
We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications.


RESULTS
Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Mechanisms include regulation of gene translocation, histone modifications, DNA methylation, DNA repair, transcription, RNA stability, alternative RNA splicing, protein degradation, gene copy number, and transposon activation. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. One of the best-studied areas of gene regulation is epigenetics, especially DNA methylation. Our examples of environmentally induced changes in DNA methylation are presented in the context of early development, when methylation patterns are initially laid down. This approach highlights the potential role for altered DNA methylation in fetal origins of adult disease and inheritance of acquired genetic change.


CONCLUSIONS
The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. Second, the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.
Edwards
Thea M
TM
Department of Zoology, University of Florida, Gainesville, Florida 32611, USA. tedwards@zoo.ufl.edu
Myers
John Peterson
JP
D000818:Animals; D003920:Diabetes Mellitus / Q000209:etiology; D004351:Drug Resistance; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D010300:Parkinson Disease / Q000209:etiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects; D012140:Respiratory Tract Diseases / Q000235:genetics