Epigenetics in type 2 diabetes

Abstract

Combinations of genetic and environmental factors contribute to the pathogenesis of type 2 diabetes (T2D); however, our knowledge of the molecular mechanisms by which these factors trigger diabetes is still limited. While genome-wide association studies have identified and characterized more than 60 genomic loci associated with T2D, recent methylome charts and reference regulatory maps obtained from tissues central to T2D can help to pinpoint the causative genetic variants. Yet, the proportion of overall trait variance explained by these genetic variants is still modest. Aging, diet, obesity, and physical inactivity represent nongenetic risk factors that may be reflected in epigenetic processes promoting T2D. Recent studies have characterized epigenetic modifications in pancreatic islets, skeletal muscle, and adipose tissue from T2D patients suggesting a central role for epigenetic mechanisms in the pathogenesis of the disease. Altered epigenetic patterns have also been found in first-degree relatives of patients with T2D and in healthy subjects born with a low birth weight suggesting that epigenetic modifications may predispose to diabetes. Lifestyle interventions including exercise and diet have also been shown to alter the epigenome in target tissues for T2D. Overall, these data propose a model where combinations of genetic, epigenetic, and nongenetic factors contribute to the risk of T2D. In this book chapter, we will explore the potential role of epigenetic mechanisms in T2D and discuss how genetics, epigenetics, and environment may interact to define the risk of developing the disease.