Epigenetic gene regulation: early environmental exposures.

Environmental epigenetics Traditional research on the combined effects of genetics and the environment investigates how individuals differ in susceptibility to disease and how susceptibility changes over time. The majority of these gene–environment interaction studies focus on genetic sequence variants, including single nucleotide polymorphisms (SNPs), which influence toxicant uptake, metabolism and subsequent disease susceptibility. Others hold genetics constant to evaluate the effects of differential nutritional, environmental and occupational exposures on health and disease. However, it has become clear that while genetics and the environment play an important role in the manifestation of many disorders, they do not fully explain all variation in human disease susceptibility. However, a growing body of evidence suggests that epigenetic gene regulation, including DNA methylation and histone modifications, are also influenced by the environment and may play a role in the fetal basis of adult disease [1]. Specifically, the ‘early origins hypothesis’ postulates that nutrition and other environmental factors during prenatal and early postnatal development program the risks for adverse health outcomes in adult life [2–4]. Developmental plasticity occurs when environmental influences affect cellular pathways during gestation, enabling a single genotype to produce a broad range of adult phenotypes [1]. Recently, human epidemiologic and animal model data have suggested that developmental plasticity is influenced by persistent epigenetic adaptations that occur early in development in response to environmental factors [5–8].