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Diabetes Research Takes a Giant Step Forward

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Leonid Kruglyak, PhD, a geneticist at Seattle's Fred Hutchinson Cancer Center, was one of the authors of an editorial accompanying the study. "It's an exciting study," Kruglyak tells WebMD. "The effort to find genes for common diseases has been going on for a decade now, but this is the first suggestion of success. If it holds up, it points out a whole new pathway for looking at diabetes that nobody has been thinking about."

The study results call for rethinking what it means to have a disease gene. A genetic disease is usually thought of a disease caused by a specific mutant gene. But for complex diseases with multiple risk factors -- such as diabetes -- genetic risk is only one part of the disease, and each genetic risk factor affects only a relatively small number of patients.

"This gene does not cause diabetes, it just increases your risk threefold," says Cox, a statistical geneticist at the University of Chicago. "We already know diabetes involves many complex environmental and genetic factors."

In other populations, the mutations appear to have the same risk -- even though they are much less common. Among European populations with exceptionally high risk of diabetes, CAPN10 mutations are responsible for only 4% of diabetes risk -- but individuals who carry the mutations have the same threefold increase in their odds of getting the disease.

"This information should be useful in finding more useful drug therapies that will be more specific for people with this genetic variation," Cox says.

Calpain expert Alfred Stracher, PhD, distinguished professor and chair of the biochemistry department at the State University of New York Health Science Center, Brooklyn, tells WebMD that the new model of how calpain may affect glucose metabolism makes sense based on what is already known about the gene.

"The results are very preliminary -- it's only when everyone is convinced that calpains are important in glucose metabolism that you could even envision medical interventions. I don't see immediate clinical applications," cautions Cox.

Kenneth M. Weiss, PhD, co-author of a commentary article in the same issue, agrees. "The authors struggle as heroically as anyone to find a causal genetic element for diabetes," he tells WebMD. "If they had a hard time, as intensely as they have looked, people should realize this is a difficult game and ... will not necessarily be meaningful in a public-health sense. My bottom line is that complex traits really are complex and really are not going to have a simple genetic solution." Weiss is professor of anthropology and genetics at Pennsylvania State University.

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