Environmental Exposures and Gene Regulation in Disease Etiology

Abstract

ObjectiveHealth 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.Data sourcesWe searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications.Data synthesisPharmaceuticals, 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.ConclusionsThe 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.

Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life

“…1 In contrast to relatively stable genetic sequences, DNA methylation patterns are dynamic in response to internal and external environmental stimuli throughout the lifecycle. 2,3 For example, demographic factors (e.g., age and gender), environmental exposures (e.g., cigarette smoking and folate intake) and genetic variations (e.g., SNPs and CNVs) all can influence DNA methylation patterns. [4][5][6][7][8] Epigenetic variations are associated with normal growth and development and with health outcomes 2,3 and diseases including obesity, diabetes, prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life.…”

“…(2) What is the longitudinal pattern of DNA methylation from birth to the first two years of life and does it vary by gender and among individuals? And (3) do cross-sectional and longitudinal patterns of DNA methylation vary across CpG and gene structures throughout the genome?…”

Mammalian foetal ovarian development: consequences for health and disease

“…Smoking, poor nutrition, pollution, pesticides, radiation, infection, drugs, etc. have been shown to be detrimental to foetal development (reviewed in de Boo & Harding (2006), Edwards & Myers (2007), Swanson et al (2009) and Langley-Evans & McMullen (2010). More recently, assisted reproductive technologies and obesity have been added to this list (Rinaudo & Lamb 2008, Freeman 2010.…”

“…More recently, assisted reproductive technologies and obesity have been added to this list (Rinaudo & Lamb 2008, Freeman 2010. The programming mechanisms by which these changes are affected is not clear, although a number of hypotheses have been proposed, notably the thrifty phenotype, oxidative stress, catch-up growth and epigenetic changes that might incorporate DNA methylation or histone acetylation (Edwards & Myers 2007, Godfrey et al 2010, Luo et al 2010.…”

Toxicogenomic Studies in Human Populations

“…can change gene regulation through a number of regulatory mechanisms (Edwards and Myers, 2007). Chemically induced changes in gene regulation are associated with complex human diseases, including cancer, diabetes, respiratory diseases, allergies, and neurodegenerative disorders.…”