The recent discovery of the major susceptibility gene for type 2 diabetes in Mexican Americans—10.6% of whom are inflicted with the disease—is being hailed as a major accomplishment. This finding, previously considered a genetic impossibility, will ultimately result in medical advancement for the treatment of type 2 diabetes.

As reported in the October issue of Nature Genetics, this breakthrough by researchers from the University of Texas-Houston Health Science Center, the University of Chicago and several supporting centers found a biochemical pathway leading to diabetes in Mexican Americans. The discovery offers a unique approach to prevention, diagnosis and treatment.

The identification of this gene is important to genetics researchers because it is the first time a genome-wide approach has successfully led to the discovery of a susceptibility gene responsible for a genetically complex disorder.

“[This] accomplishment is a tour de force,” says Dr. Allen Spiegel, director of the National Institute of Diabetes and Digestive and Kidney Diseases. “Actually identifying susceptibility genes for diseases such as diabetes has proved exceedingly difficult. [This discovery] is exciting for all individuals suffering from type 2 diabetes because it will lead to a greater understanding of the pathogenesis of type 2 diabetes and possibly to new forms of treatment.”

Researchers have found it particularly difficult to isolate the genes responsible for type 2 diabetes, because diabetes is not a single disease but a group of related disorders with similar symptoms. In addition, because type 2 diabetes is typically diagnosed after age 40 and results in a shortened life span, it has been hard to gather information from the large multi-generation families that are normally used for genetic studies.

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However, this obstacle was overcome with the help of the Human Genetics Center of the University of Texas-Houston. The Human Genetics Team spent nearly 20 years studying and working with a community of Mexican Americans in Starr County, Texas—a group with very high rates of diabetes. The team provided extensive family histories, clinical data and DNA samples from 330 pairs of brothers and sisters affected by diabetes.

“People kept telling us it was impossible,” recalls research team leader Graeme Bell, a professor of biochemistry, molecular biology and medicine at the Howard Hughes Medical Institute at the University of Chicago.

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While this genetic variation on its own does not cause diabetes, the gene interacts with lifestyle factors such as diet and exercise to put people at greater risk of developing the disease.

The combination “is not the whole story of genetic liability,” Bell says. “But we think it accounts for about 14% of the risk in Mexican Americans and about 4% in Europeans.”

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