Our bodies have to regulate the level of glucose, or sugar, in the blood. The hormone insulin, produced by beta cells in the pancreas, is crucial to that regulation. Type 1 diabetes is sometimes caused by problems with the immune system that lead to the destruction of beta cells and the loss of insulin. Small genetic changes have been linked to the disorder, and can explain about 40 to 50 percent of the genetic causes of type 1 diabetes. But genetic changes haven't been found in every case. New work has reviewed some of the epigenetic influences that can contribute to type 1 diabetes.
Epigenetics can affect gene activity without changing the genetic sequence, and environmental influences can impact epigenetics. These environmentally-induced epigenetic changes have been linked to type 1 diabetes in various research studies.
Type 1 diabetes has been known to be connected to the HLA gene region since the 1970s; dozens of mutations in the DNA sequence in that region have since been linked to the disorder. An epigenetic feature known as methylation in the HLA region has also been associated with type 1 diabetes.
DNA has to be compacted and carefully organized in the cell; its three-dimensional structure can affect gene expression, and DNA is wound around histone proteins. Histone modifications are another epigenetic feature of the genome. Abnormal histone modifications have also been identified in type 1 diabetes patients.
Non-coding RNAs, which are sometimes involved in gene regulation, have also been associated with type 1 diabetes.
The expression of immunological and inflammatory genes and the function of beta cells in the pancreas may be affected by any or all of these epigenetic changes, which influence the development of type 1 diabetes in many ways.
"Given the relationship between epigenetic changes and type 1 diabetes, various epigenetic changes could serve as markers for disease progression and treatment effects or even as targets for future therapeutics. For example, noncoding RNAs can be measured noninvasively, while changes in DNA methylation levels and patterns for particular genes could indicate that a genetically predisposed person is developing type 1 diabetes," explained study co-author Dr. Cong-Yi Wang of the Huazhong University of Science and Technology.
Other studies have suggested that drugs that change DNA methylation might benefit type 1 diabetics.
"Based on existing literature, it is clear that environmental insult-induced epigenetic changes modulate the expression of critical genes relevant to the initiation and progression of autoimmunity and beta cell destruction and are therefore implicated in the development of type 1 diabetes," concluded study co-author Dr. Fei Xiong, also of the Huazhong University of Science and Technology.