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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
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