The Role of Epigenetics in Type 1 Diabetes

PURPOSE OF REVIEW: Epigenetics is defined as mitotically heritable changes in gene expression that do not directly alter the DNA sequence. By implication, such epigenetic changes are non-genetically determined, although they can be affected by inherited genetic variation. Extensive evidence indicates that autoimmune diseases including type 1 diabetes are determined by the interaction of genetic and non-genetic factors. Much is known of the genetic causes of these diseases, but the non-genetic effects are less clear-cut. Further, it remains unclear how they interact to cause the destructive autoimmune process. This review identifies the key issues in the genetic/non-genetic interaction, examining the most recent evidence of the role of non-genetic effects in the disease process, including the impact of epigenetic effects on key pathways. RECENT FINDINGS: Recent research indicates that these pathways likely involve immune effector cells both of the innate and adaptive immune response. Specifically, there is evidence of cell type-specific enrichment in altered DNA methylation, changes which were temporally stable and enriched at gene regulatory elements. SUMMARY: Epigenomics remains in its infancy, and we anticipate further studies will define how the interaction of genetic and non-genetic effects induces tissue-specific destruction and enhances our ability to predict, and possibly even modify that process.