Studies Uncover New Genes Boosting Type 2 Diabetes Risk

Researchers have identified 10 genetic variants that may make type 2 diabetes more likely and may lead to new treatments for type 2 diabetes. Scientists have found several new genes that appear to increase the risk for developing type 2 diabetes. Researchers say these findings bring to 10 the number of genes suspected in increasing the odds for type 2 diabetes, the most common, obesity-linked form of the disease. Understanding how these genes contribute to the disorder may lead to new strategies for prevention and treatment.

In the first paper in Nature Genetics, a team led by Dr. Kari Stefansson, CEO of deCODE Genetics, report on a new genetic risk factor for type 2 diabetes.

The researchers conducted a large survey in Iceland comparing the frequencies of several hundred thousand common genetic variants in healthy people against those who have the disease.  They found that the CDKAL1 gene was associated with type 2 diabetes. "It affects the secretion of insulin," Stefansson said. "So people with this variant secrete less insulin in response to glucose than people in the general population."

In addition, they saw the same association between type 2 diabetes and a variant in the CDKAL1 gene in other populations of Europeans and Han Chinese.

According to Stefansson, people with two copies of the risk variant were found to face a 50 percent increased risk of developing the disease when compared with people with only a single copy of the gene variant. About 25 percent of the population has this variant, Stefansson said.

People with two copies of the gene variant produce about 20 percent less insulin in response to rising blood sugar than those with only one copy or non-carriers. This suggests that the variant increases the risk for type 2 diabetes by reducing insulin production.

Stefansson’s company has developed a test to identify people with the gene variant. Their hope is to be able to identify people at risk for type 2 diabetes so that they can be counseled to make lifestyle changes or started on medication before the condition develops.

In addition to confirming several gene variants previously tied to type 2 diabetes, the researchers found three new variants — CDKN2A and CDKN2B — lying on chromosome 9, and IGF2BP2 on chromosome 3, that are also linked to the disease.
"We are now able to confidently identify genetic risk factors for type 2 diabetes," said Michael Boehnke, the Richard G. Cornell Collegiate Professor of Biostatistics at the University of Michigan, and coauthor of one of the Science papers.
At least 10 gene variants have now been linked to type 2 diabetes, each exerting a modest effect on risk. The list will likely continue to grow, while the current genes that have been pinpointed provide a valuable starting point for understanding the disease.

"These genes are not telling the entire genetic story of type 2 diabetes," Boehnke cautioned. "This is a small part of the overall picture, which includes environment and behavioral factors." However, he added, knowing the genetics of type 2 diabetes could lead to new targeted therapies.

Kari Stefansson, M.D., CEO, deCODE Genetics, Reykjavik, Iceland; Larry Deeb, M.D., president, medicine and science, American Diabetes Association, Chicago; Michael Boehnke, Ph.D., Richard G. Cornell collegiate professor, biostatistics, University of Michigan, Ann Arbor; April 26, 2007, Nature Geneticsonline, April 26, 2007,Scienceonline; MIT news release.

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