Gene for Diabetes Found in 40% of Population

Scientists have discovered a variant gene that leads to a sizable extra risk of Type 2 diabetes and is carried by more than a third of the American population.

The finding is being reported in the January journal Nature Genetics by researchers at Decode Genetics, a company in Reykjavik, Iceland, that specializes in finding the genetic roots of human diseases. Decode Genetics first found the variant gene – one of many different versions that exist in the human population – in Icelanders and has now confirmed the finding in a Danish and an American population.

An immediate practical consequence of the discovery, said Decode’s chief executive, Kari Stefansson, would be to develop a diagnostic test to identify people who carry the variant gene. If people knew of their extra risk, they would have an incentive to stay thin and exercise, he said.

Because people carry two copies of every gene, one inherited from each parent, the risk conferred by the new gene depends on whether one or two copies of it have been inherited. The estimated 38 percent of Americans who have inherited a single copy have a 45 percent greater risk of Type 2 than do unaffected members of the population. The estimated 7 percent who carry two copies are 141 percent more likely to develop the disease, according to the Decode researchers, who were led by Struan F. A. Grant.

What scientists call the "population-attributable risk" of the new variant is 21 percent, which means that if all the variant genes in the population were erased, so would be 21 percent of diabetes cases.

"In terms of the epidemiological risk of diabetes, this is by far the biggest finding to date," he said, just after hearing a lecture on the finding by Augustine Kong, Decode’s chief statistician. Diabetes is thought to be caused by a variety of different genes, each conferring a risk for the disease. Because most of the variants exert a minor effect, they are hard to detect, and many claims to have found diabetes-causing genes have turned out to be unfounded.

"This has turned out to be the disease that has been the most difficult for geneticists to crack, probably because of the large environmental contribution," Dr. Stefansson said.

The new variant identified by Decode was of a somewhat obscure gene that had not been suspected of having any involvement in diabetes. The gene, designated TCF7L2, is one that controls the activity of other genes. Its role may include setting the level of a hormone that acts along with insulin to control blood sugar levels.

Discovery of the TCF7L2 gene could be therapeutically helpful, Dr. Stefansson said, because it identified a major biochemical chain reaction or pathway through which the disease developed. Several different genes, and their protein products, are involved in the pathway that sets the level of the companion hormone. Any of these genes and proteins are potential targets for new drugs.

He said he could not yet say if the genetic variant was more common in African-Americans and so might explain their greater burden of Type 2 diabetes. But he noted that the variant was ancient, having arisen before the dispersal of modern humans from Africa some 50,000 years ago, and would probably be found to exist to varying degrees in all populations.

journal Nature Genetics, Jan. 2006

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