New gene associated with type 1 diabetes

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Public release date: 22-Jul-2004

Baylor College of Medicine

New gene associated with type 1 diabetes

HOUSTON ‹ A new gene mutation identified by researchers at Baylor College of

Medicine (BCM) in Houston is part of the constellation of genes associated

with susceptibility to developing type 1 diabetes. It could also play a role

in the devastating complications of diabetes such as kidney failure.

The gene called SUMO-4 contributes a portion of the risk of getting this

form of diabetes, which typically strikes youngsters, said Drs.

Owerbach, Kurt Bohren and Gabbay. Owerbach and Bohren are associate

and assistant professors in the section of molecular diabetes and metabolism

in the department of pediatrics at BCM, respectively. Gabbay is professor of

pediatrics and head of the section.

SUMO-4 plays a role in regulating the immune system. When mutated, the gene

functions abnormally, prolonging the inflammatory response.

This finding gives scientists a clue about the autoimmune cause of diabetes.

In type 1 diabetes, the body's protective system is turned against its own

insulin-producing alpha cells in the pancreas. As a result, people who have

type 1 diabetes do not produce insulin. Without insulin, their bodies cannot

regulate the levels of sugar in their blood.

The mutated SUMO-4 gene may influence the inflammatory process itself and

increase the susceptibility to the complications of diabetes.

The reports of the work by Owerbach, Bohren and Gabbay and the rest of their

team in the Harry B. and Aileen B. Gordon Diabetes Research Center at Texas

Children's Hospital and BCM appeared in the June 25, 2004 issue of the

Journal of Biological Chemistry and the July 2004 issue of the journal

Diabetes.

No single gene causes type 1 diabetes. However, the BCM researchers and

others in the field have identified a host of genes that contribute to the

risk of developing the disease. Among the most potent genes are those in the

HLA or human leukocyte antigen region, which regulate the immune system and

help immune cells differentiate self from non-self.

Gene variants of DR and DQ in the HLA region are particularly important and

are found in 95 percent of type 1 diabetics. Together, the genes in the HLA

region account for as much as 40 percent of the familial risk of developing

type1 diabetes. A second set of Type 1 diabetes susceptibility genes have

also been identified in the region immediately preceding the insulin gene.

This region contains a VNTR or variable number of tandem repeats, which

refers to repeats of specific chemical bases that make up DNA. Inheritance

of certain VNTR's increases the risk of developing type 1 diabetes.

SUMO-4 contributes to the overall risk. However, the significance of the

SUMO-4 gene lies in its role in controlling the immune and inflammatory

response. The diabetes-associated variant gene appears to increase the

stress response and cell death. SUMO-4 may provide a therapeutic target to

modify or curtail the inflammatory process leading to the destruction of the

alpha cells.