New Methylation Patterns in Type 1 Diabetes Detected

Scientists at Helmholtz Zentrum München have investigated methylation patterns of risk genes for type 1 diabetes. In the ‘Journal of Autoimmunity’ they report a strong methylation signal in the HLA region, which persists throughout life and leads to correspondingly lower levels of HLA-DR protein. In addition, the authors show that a methylation signal on another gene could potentially serve as a marker of autoimmunity.

Increasingly, the scientific consensus is that not only genes are responsible for the development of diseases, but also what happens around these genes - epigenetics. For example, the attachment of methyl groups to genes, which therefore get read less often, plays an important role in this process. Obviously, this principle also applies to type 1 diabetes, as researchers of the Institute for Diabetes Research (IDF) and the Institute of Computational Biology (ICB) at Helmholtz Zentrum München show in collaboration with researchers from Dresden and the United Kingdom. For their study, the scientists investigated samples of several prospective type 1 diabetes cohorts. “Generally speaking, it can be said that all 45 of the risk genes we studied for type 1 diabetes showed associations with high methylation rates," explained first author Dr. Alida Kindt. “We were then particularly interested in the methylation of the HLA-DR gene, which is significantly involved in the development of autoimmune diseases.”*The authors found that certain methylations in the HLA-DR region occurred especially in gene variants that indicate an increased risk of type 1 diabetes. "The corresponding pattern was found both in newborns, in toddlers and in adults, and was associated with lower expression of the HLA-DR gene," said Kindt. In addition, the scientists noticed a new methylation signal on the gene for the L-lactate dehydrogenase C chain (LDHC). "This was previously unknown and could potentially be a marker to screen patients for a possible type 1 diabetes risk," said Kindt.The study was led by Professor Anette-G. Ziegler from the IDF and Ezio Bonifacio, director of the DFG Research Center for Regenerative Therapies (CRTD) at TU Dresden, who comments: "Our research provides new insights into the development of autoimmunity and type 1 diabetes. We had no idea that the genetics underlying type 1 diabetes would be associated with such consistent and profound effects on methylation within the gene. We are particularly interested to see if these effects are at all modifiable by environment and treatment.”Further Information* The gene HLA-DR (human leukocyte antigen - DR) encodes an MHC class II surface receptor. Its main function is to present to the immune system peptide antigens possibly of foreign origin. This leads to the triggering or suppression of T (helper) cell responses, which eventually lead to the production of antibodies to the antigen.

Original publication:
Kindt, A.S.D. et al. (2017): Allele-specific methylation of type 1 diabetes susceptibility genes. Journal of Autoimmunity, DOI: 10.1016/j.jaut.2017.11.008