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Gene Provides New Hints to Type 1 Diabetes Development

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Gene Provides Hints to Type 1 Diabetes Development

Gene Provides New Hints to Type 1 Diabetes Development

December 20, 2007

By: Diana Barnes-Brown for Diabetes1

Researchers in Florida and the United Kingdom have discovered a correlation between susceptibility to type 1 diabetes and lower concentrations of a genetic biomarker for immune activation present in the blood. These findings may be instrumental to unlocking the secrets of the autoimmune attacks that cause type 1 diabetes.

The results of the research are printed in the journal Nature Genetics, in a study written by Christopher Lowe, Jason Cooper, and co-researchers at the Juvenile Diabetes Research Foundation/Welcome Trust Diabetes and Inflammation Laboratory and from the University of Florida.
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Another genetic research method that has proven helpful in diabetes research is known as genome wide association (GWA), which compares genetic anomalies of various diseases with one another. GWA has recently uncovered a link between type 1 diabetes and Crohn’s disease, which affects the digestive tract.

The discovery came out of a large-scale analysis of genetic samples from patients with type 1 diabetes. The research establishes a link between type 1 diabetes risk and lower levels of the IL2RA blood protein, which is an immune cell receptor that regulates immune system functioning.

The mechanism that may cause IL2RA to impact type 1 diabetes risk was suggested by a study in mice, conducted earlier this year. In the study, researchers found that mice’s susceptibility to diabetes is caused partly by reduced production of the mouse version of the protein that binds to the IL2RA receptor in immune T cells.

In the mouse study, the researchers were able to demonstrate that when the gene for the protein, known as mIL-2, is not functioning properly, a type of T cell called regulatory T cells do not develop as they should. They fail to prevent the body’s immune system from attacking insulin-producing cells in the pancreas. The new research on IL2RA biomarkers in humans is evidence of a similar pathway in people who have type 1 diabetes.

Specifically, the researchers found that when the IL2RA protein binds to the signaling protein IL-2, the receptor is then released into the blood, where it can be measured by researchers. In addition, people at risk for developing type 1 diabetes have lower levels of the IL-2 protein. This discovery suggests that some variants of the IL2RA gene may lead to insufficient levels of the protein receptor.

The next question that must be answered by researchers is whether there is something that interferes with the proper interaction between IL-2 and IL2RA, and thus prevents normal regulatory T cell development.

Mapping the genes and gene variants responsible for various diseases onto the human genome has been a topic of interest to medical researchers for many years. By understanding the source of disease, a cure may be possible through genetic therapy.

This study represents an important step forward in the search for a cure, because the confirmation of a link between the gene variant and an observable trait (that is, the presence of different IL2RA protein levels in the blood) will allow the diabetes research community to further focus its efforts.


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