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Immune System Genes Show Links to Type 1 Diabetes
Date:9/8/2010

By Serena Gordon
HealthDay Reporter

WEDNESDAY, Sept. 8 (HealthDay News) -- The exact cause of type 1 diabetes is still unknown, but international researchers have found a link between the blood sugar disorder and a network of immune system genes.

Using a genome-wide association study, the researchers found that a certain group of genes that react in response to viral infections were present in both rats and humans, and that those same genes were also associated with a susceptibility to type 1 diabetes.

"Diseases arise as a result of many genetic and environmental factors through gene networks that cause tissue damage," explained study senior author Dr. Stuart Cook, the group head of molecular and cellular cardiology at the Medical Research Council Clinical Sciences Centre, and a professor of clinical and molecular cardiology at Imperial College in London.

"We used an approach to identify the major control points' central command of an inflammatory gene network. This led us to uncover hundreds of new genes that might cause diabetes and one major control gene that controls the whole network," said Cook.

He added that one of the genes belongs to a class of genes that might make a good target for drug therapy in the future.

Results of the study are published in the Sept. 9 issue of Nature.

Each year, more than 30,000 people are diagnosed with type 1 diabetes, formerly known as juvenile diabetes, according to the Juvenile Diabetes Research Foundation (JDRF). People with type 1 diabetes no longer produce enough of the hormone insulin to effectively use the sugars found in carbohydrate-containing foods. To survive, people with type 1 diabetes must take insulin injections or use an insulin pump for the rest of their lives.

Experts believe the disease is an autoimmune disease, which means that the body's immune system mistakenly turns against healthy cells, such as the insulin-producing cells in the pancreas, and destroys them. People who develop type 1 diabetes are believed to have a genetic susceptibility to the disease that's then triggered by something in the environment, possibly a virus.

In the current study, the researchers didn't initially set out to look for type 1 diabetes genes. They started out by looking at a certain group of genes in rats, in this case a network of genes controlled by a gene called interferon regulatory factor 7 (IRF7). IRF7 is like a master switch that controls the genes in its network. The entire network of genes controlled by IRF7 is called the IRF7-driven inflammatory network (IDIN).

The researchers discovered that when there were differences in IRF7, there were also differences in the way other genes expressed themselves.

Cook and his colleagues then searched for a network of genes in humans that might behave the same way. They found an area on chromosome 13q32 that is controlled by a gene called the "Epstein-Barr virus induced gene 2" (Ebi2). This gene appeared to be the human equivalent of the IRF7 gene in rats.

Within this human version of the IDIN, research found a gene called IFIH1, which has been found in other research to be associated with the development of type 1 diabetes.

"Usually, research starts from the genetics and goes to function. Here, they started with a function -- [an immune system reaction] -- and were looking for a gene," explained Marie Nierras, director of research and scientific affairs for the JDRF.

"The value of such a result is that if you can get to the same place using more than one pathway, it tends to support the hypothesis," she said.

In this case, the hypothesis supported is the idea that type 1 diabetes may be triggered by an immune system response to a virus. However, Nierras stressed that this study doesn't conclusively prove that a virus is the trigger for type 1 diabetes.

"We know better today that this network of genes is involved, and with a network, you have many targets you can test. This research invites us to plan experiments going forward, and opens up many more questions, like 'If I disrupt this branch of the network, do I disrupt diabetes?' Or, 'If you look back at previous research knowing this study's results, does that help to better explain previous results?'" said Nierras.

Cook said this type of genome-wide association study can be used for other diseases as well, and that his team is hoping to eventually develop a new drug based on the genetic target they discovered.

More information

Learn more about type 1 diabetes and its causes from the U.S. National Library of Medicine.

SOURCES: Stuart Cook, M.D., Ph.D., group head, molecular and cellular cardiology, the Medical Research Council Clinical Sciences Centre, and professor, clinical and molecular cardiology, Imperial College, London; Marie Nierras, Ph.D., director, research and scientific affairs, Juvenile Diabetes Research Foundation, New York City; Sept. 9, 2010, Nature


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