A new gene mutation, identified by researchers at Baylor College of Medicine in Houston, is part of the constellation of genes associated with susceptibility to developing type 1diabetes. It could also play a role in the devastating complications of diabetes such as kidney failure, said a release from Baylor College of Medicine.

The gene called Sumo-4 contributes a portion of the risk of this form of diabetes, which typically strikes youngsters, said Dr. David Owerbach, Dr Kurt Bohren and Dr Kenneth Gabbay.

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 1diabetes, the body's protective system is turned against its own insulin-producing ß cells in the pancreas. As a result, people who have type 1diabetes do not produce insulin. Without insulin, their bodies cannot regulate the levels of sugar in their blood, the release said.

The mutated Sumo-4 gene may influence the inflammatory process itself and increase the susceptibility to the complications of 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 variable number of tandem repeats (VNTR), 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 ß cells, the release added.

The reports of the work appeared in the June 25, 2004 issue of the Journal of Biological Chemistry and the July 2004 issue of the journal Diabetes.