new cluse to diabetic link

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Immune System Genes Show Links to Type 1 Diabetes

Sep 13, 2010

This press release is an announcement submitted by NIH, and was not written

by Diabetes Health.

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.

* * *

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