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Researchers Uncover Gene That Raises Risk for Type 1 Diabetes

A discovery at the Barbara Davis Center for Childhood Diabetes has identified a genetic risk for type 1 diabetes three to four times higher than previously thought possible.// Researchers have found evidence of an additional gene – gene X – in the human leukocyte antigen (HLA) region on chromosome 6 that raises the risk for type 1 diabetes autoimmunity to an astounding 80 percent.

It has been known for some time that approximately 5 percent of individuals with known high risk genes in the HLA region on chromosome 6 will develop type 1 diabetes – a region comprised of more than 220 genes. Past research identified specific HLA-DR and HLA-DQ genes as genetic markers that when passed on to offspring of a diabetic parent determined a risk for type 1 diabetes in a child. Investigators have been searching for other genes determining diabetes risk, looking primarily at genetic regions outside of the HLA region. The current research from the Barbara Davis Center evaluated the influence of additional genes in the HLA region.

Beginning in 1993, more than 30,000 newborns in Colorado were genetically typed at birth through the Diabetes Autoimmunity Study in the Young (DAISY), a study led by Dr. Marian Rewers, clinical director of the Barbara Davis Center. Those with high risk HLA-DR and HLA-DQ genes were followed and monitored for the development of anti-islet cell autoimmunity in the pancreas (pre-diabetes) and diabetes.

“By combining measurement of high risk HLA-DR and HLA-DQ genes with defined family analysis we found that type 1 diabetes is more a Mendelian genetic disease that follows the basic principles of heredity,” said George Eisenbarth, MD, PhD, executive director of the Barbara Davis Center for Childhood Diabetes. “We found an extreme risk – greater than 80 percent – determined at birth by combining HLA-DR and HLA-DQ genetic typing with inheritance of other genes in the HLA region of chromosome 6. This research indicates an unexpec ted genetic determination of type 1 diabetes with a major unknown genetic locus and suggests that future research should concentrate on defining the additional genes in the HLA region that cause diabetes.”

The research also brings to light a possibility to prevent childhood diabetes in the future. The authors indicate that “infants and children who have the highest genetic risk for diabetes as defined by this study are an important group that may now be considered for initial clinical trials to prevent childhood diabetes before the development of anti-islet autoantibodies.”

In the meantime, parents should be alert to the symptoms of type 1 diabetes usually first seen in childhood. Symptoms can include extreme thirst, frequent urination, and rapid weight loss. If symptoms are left unchecked, an onset of diabetes could be fatal.

“If a child is severely ill with an unknown cause, parents should think about diabetes,” Eisenbarth said. “A child can be easily tested for diabetes. If a diagnosis is delayed at the onset of diabetes, children can die – it is preventable if children are tested.” Eisenbarth indicated there is a national trial organization that tests relatives of patients with diabetes for risk.



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