Researchers from Stanford University have revealed that type 1 diabetes may not be due to bad genes but rather to good genes behaving badly.
Previous studies in identical twins have revealed that often one twin develops type 1 diabetes while the other twin remains disease-free, this may be due to how genetically at-risk individuals respond differently to environmental stimuli.
In some cases, the immune system will respond in a benign fashion, while in other cases it will begin an inflammatory response that can ultimately lead to diabetes.
During the study, the research team led by C. Garrison Fathman, M.D., studied differences in gene expression between two groups of mice.
The first group, non-obese diabetic mice, spontaneously develop type 1 diabetes.
The second group, mice genetically identical to the first group except for their MHC genes, responsible for causing diabetes.
The researchers looked at gene expression in three different tissues in the diabetic and non-diabetic mice at separate times after birth.
In the first few weeks of life, they found an explosion of changes in gene expression in the pancreatic lymph nodes, spleen and circulating blood cells of the diabetic mice compared with those in the non-diabetic mice.
At 8 weeks, this activity had quieted down. But several weeks later, when the mice were 12 weeks old, a second explosion of changes in gene expression occurred in the diabetic mice in all three tissues examined: pancreatic lymph nodes, spleen and blood cells.
According to Dr. Fathman, the results suggest that type 1 diabetes may not result from genetic mutations but from differences in how normal genes and gene variants are turned on and off during disease progression.
In addition to identifying altered genes that may indicate potential avenues for therapeutic or preventive treatments, the authors also found patterns of coordinated gene expression that may prove useful as biomarkers of disease onset or progression.
The study was supported by the National Institute of Allergy and Infectious Diseases, (NIAID) part of the National Institutes of Health.