Epigenetics and the exposomes: Obesity and beyond

Abstract

ABSTRACTThe specific genetic alterations that result in diseases and complex syndromes have been and continue to be identified. Search for the origins of disease have led to investigations into the roles of dietary and environmental factors as potential triggers or modifiers of risk. Genome-wide association studies have identified concepts such as the rare variant-common disease hypothesis and the common variant-common disease hypothesis.1 Through association studies, unique gene-environment interactions, which may occur with or without specific periods of permissiveness or vulnerabilities, have also been identified. Major conditions where the role of exposomes and epigenetics are rapidly evolving are obesity, neurological disorders, immune disorders and cancers. These concepts are particularly intriguing in the context of obesity. BACKGROUND: Epigenetics can be defined as heritable traits resulting from changes in DNA or chromatin structure without alterations in the DNA sequence.2 Nutritional epigenetics is seen as a means for the prevention of developmental diseases and cancer, and to delay processes associated with aging.3,4 Diseases in which epigenetic factors are considered significant include type 2 diabetes mellitus, obesity, inflammation, cardiovascular diseases, neurocognitive disorders, and immune diseases, with neural function influenced by environmental factors including early experience.5 Studies with rodent models suggest that during both early development and in adult life, environmental signals can activate intracellular pathways that directly remodel the epigenome, leading to changes in gene expression and function. These studies define a biological basis for the interplay between environmental signals and the genome in the regulation of individual differences in behavior, cognition, and physiology.6 In reproduction, certain genes are turned on while others are turned off in the process of imprinting. In the case of imprinting, even though there are two copies of the gene, only one copy is expressed and there is no substitute functional allele. For this reason, imprinting makes the imprinted genes more vulnerable to the negative effects of mutations.7