Genetic and epigenetic factors in etiology of diabetes mellitus type 1

Pediatrics. 2013 Dec;132(6):1112-22. doi: 10.1542/peds.2013-1652. Epub 2013 Nov 4.


Diabetes mellitus type 1 (T1D) is a complex disease resulting from the interplay of genetic, epigenetic, and environmental factors. Recent progress in understanding the genetic basis of T1D has resulted in an increased recognition of childhood diabetes heterogeneity. After the initial success of family-based linkage analyses, which uncovered the strong linkage and association between HLA gene variants and T1D, genome-wide association studies performed with high-density single-nucleotide polymorphism genotyping platforms provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remains to be performed. T1D is one of the most heritable common diseases, and among autoimmune diseases it has the largest range of concordance rates in monozygotic twins. This fact, coupled with evidence of various epigenetic modifications of gene expression, provides convincing proof of the complex interplay between genetic and environmental factors. In T1D, epigenetic phenomena, such as DNA methylation, histone modifications, and microRNA dysregulation, have been associated with altered gene expression. Increasing epidemiologic and experimental evidence supports the role of genetic and epigenetic alterations in the etiopathology of diabetes. We discuss recent results related to the role of genetic and epigenetic factors involved in development of T1D.

Keywords: Type 1; diabetes mellitus; epigenetics; etiology; genetics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / genetics*
  • Epigenesis, Genetic*
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • HLA-D Antigens / genetics
  • Humans
  • Polymorphism, Single Nucleotide


  • Genetic Markers
  • HLA-D Antigens