Type 2 diabetes has a broad reach: it can wreak havoc on many different organs, including the eyes, the kidneys and the heart, and it affects some 135 million people worldwide. But it doesn't do so at random. Individuals are rendered more susceptible by environmental factors such as diet and by complex sets of genetic influences. Researchers have had a hard time unraveling the latter part of that risk equation, because a single gene isn't to blame. But now they have found a gene that's definitely at least partially at fault.

Having screened Mexican Americans and Finns prone to type 2 diabetes, Howard Hughes Medical Institute investigator Graeme Bell and his colleagues at the University of Chicago uncovered single-nucleotide polymorphisms (SNPs) in the gene for calpain-10 on chromosome 2, which they describe in the October issue of Nature Genetics. A related paper in the Journal of Clinical Investigation from the same authors and scientitsts at the National Institutes of Health reveals the same calpain-10 SNP in a high-risk population of Pima Indians. "This was the first genome-wide screen for susceptibility genes for type 2 diabetes," Bell says. "Such an identification had never been done before for such a genetically complex disorder."

The find is somewhat unexpected because calpain-10 produces a protein-snipping enzyme when expressed--not something that anyone had guessed might be involved with diabetes. More surprising still, although Bell's team confirmed that low levels of this protein do correlate to an increased risk for type 2 diabetes, the SNP they found on the gene isn't within the region of calpain-10 that encodes that protein. "Clearly, once we understand more about the pathway, it could lead to new therapeutic approaches for treating diabetes," Bell adds. "But we don't know enough about the pathway right now to predict whether or not that realization will come to pass."