Epigenetics and Diabetes Risk: Not Just for Imprinting Anymore?
2011; American Diabetes Association; Volume: 60; Issue: 7 Linguagem: Inglês
10.2337/db11-0515
ISSN1939-327X
Autores Tópico(s)Birth, Development, and Health
ResumoRelationships of maternal obesity, diabetes, and nutrition during pregnancy with birth weight and in turn relationships between birth weight and risk of obesity and diabetes in later life have long been observed (rev. in 1). Elucidating the etiology of these relationships is challenging given that mammalian mothers impart both genes and intrauterine environment to their offspring. One factor that may play a role is epigenetics. Epigenetic effects are defined as heritable changes to DNA structure that do not involve changes to the DNA sequence. Unlike sequence changes, they can be reset or undone under certain conditions such as in early development. Mechanisms include changes in histone deacetylation and methylation of cytosines in CpG clusters (2). An epigenetic phenomenon that is well-documented in humans and may be the first that springs to mind is genomic imprinting, whereby during germ cell development, regulatory regions of certain genes are differentially methylated and expressed depending on whether the gene is inherited from the mother or father (2). Imprinting impacts several genes, including some in which mutation of the expressed copy or disturbance of normal imprinting is involved in both most cases of the rare transient neonatal form of diabetes (3) and, based on recent evidence, apparently some cases of polygenic type 1 (4) and 2 (5) diabetes as well. However, other factors, including environmental stimuli, can induce epigenetic changes as well (6–8); thus imprinting is not the only epigenetic mechanism potentially involved in diabetes and the related phenotypes of obesity and metabolic syndrome (9). Moreover, imprinting is not the only example of the phenomenon of …
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