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Genetic mutation found that is major contributor to type 1 diabetes

A natural mutation of a gene that helps regulate the reactivity of the immune system is a major contributor to type 1 diabetes, Medical College of Georgia researchers have found.

The newly discovered gene, SUMO-4, controls the activity of NFκB, a molecule that in turn controls the activity of cytokines, proteins that regulate the intensity and duration of the immune response, according to research that will be published in the August print issue of Nature Genetics and online July 11.

By examining the transmission of genes from parents to children in nearly 1,000 diabetic families from around the world, the researchers found that a certain natural mutation of that SUMO-4 gene increases the risk of type 1 diabetes.

"This helps us understand how type 1 diabetes works, and we can use this improved understanding to better predict who will get the disease and design new intervention strategies for those who do," said Dr. Jin-Xiong She, director of the MCG Center for Biotechnology and Genomic Medicine and a co-senior author on the study.

"The mutation we have found is going to increase the responsive capacity of the immune system to environmental triggers or stimulators; it makes it more reactive," said Dr. Cong-Yi Wang, molecular geneticist and co-senior author.

Dr. Wang and his research team found that when that mutation encounters an environmental trigger, such as a bacterial or viral infection, it throws off the usual well-balanced activity of the immune system, initiating an autoimmune response that eventually attacks the patient's own tissue.

They already are exploring the gene's potential role in other autoimmune diseases as well such as lupus, thyroid disease, arthritis and multiple sclerosis.

SUMO-4 is the fourth gene identified that contributes to type 1 diabetes, taking a place just behind HLA, another regulator of immunity, in terms of relative risk. "Many genes are involved in type 1 diabetes, but
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
11-Jul-2004


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