Integrating Transcriptome and Epigenome: Putting Together the Pieces of the Type 2 Diabetes Pathogenesis Puzzle

  1. Swapan Kumar Das
  1. Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC
  1. Corresponding author: Swapan Kumar Das, sdas{at}wakehealth.edu.

The complex pathophysiological process of type 2 diabetes (T2D) involves perturbation of gene expression, leading to derangement of multiple physiological processes in tissues that are important in glucose homeostasis (1). Interactions of environmental factors with genetic and epigenetic variants are likely to play an important role; however, the relative contribution of each component to gene expression linked to T2D pathogenesis could differ among individuals. Understanding the molecular mechanisms underlying this interaction is crucial for developing novel therapeutic and preventative strategies for T2D.

Incomplete concordance of T2D in monozygotic (MZ) twins (considered genetically identical) is indicative that nongenetic/environmental factors can play a prominent role in T2D susceptibility and pathogenesis (2). During pre- and postnatal life, environmental factors (including dietary factors) in each tissue microenvironment interact with cellular genetic regulatory architecture and may modulate gene expression. Environmental factors also may modulate gene expression by causing epigenetic modifications of the genome, including DNA methylation (Fig. 1). Thus, tracing molecular events through layers of biological information, including DNA methylation, gene expression, genotype, and physiological data, is required for solving the puzzle of the etiology of T2D.

Figure 1

A causal model of T2D pathogenesis. Environmental factors (including dietary factors) may modulate the expression of genes by interacting with cellular genetic regulatory architecture or by causing epigenetic modifications of the genome, including DNA methylation. Perturbation of gene expression in tissues important for glucose homeostasis causes derangement of multiple physiological processes and leads to the pathogenesis of T2D. An integrative functional ‘omics paradigm that traces molecular events through layers of biological information is required for solving the puzzle of the etiology of T2D. epiSNP, methylation and other epigenetic regulatory single …

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  1. doi: 10.2337/db14-0757 Diabetes vol. 63 no. 9 2901-2903
  1. Free via Open Access: OA

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