Gene that predisposes to type 2 diabetes discovered

Researchers with deCODE Genetics in Iceland report discovery of a gene variant that substantially increases the risk for type 2 diabetes, opening the door to new diagnostics and therapeutics for this common disease, the researchers say

The variant, found in the transcription factor 7-like 2 (TCF7L2) gene, may account for up to 21% of the population-attributable risk for type 2 diabetes, they report. “That is very substantial for type 2 diabetes,” Dr Kari Stefansson, founder of deCODE Genetics, located in Reykjavik, Iceland, and senior author on the paper, told heartwire. “Type 2 diabetes has turned out to be most difficult for human geneticists to crack because of the fact there is a large environmental contributor to the risk,” principally obesity, he added, “so we are very proud of having been able to crack this.”Results of their work were published online January 15, 2006 as a letter in Nature Genetics. First author on the paper is Dr Struan FA Grant (deCODE Genetics). Variant confirmed in three populations Researchers in this group previously reported “suggestive linkage” in type 2 diabetes to chromosome 10q, the authors write. For this report, they genotyped 228 individuals in Iceland and isolated a variant of the TCF7L2 gene on chromosome 10q associated with an increased risk for diabetes in this population. They then replicated their finding in two other populations, one in Denmark, and the other in the US, through the University of Pennsylvania. They report that compared with noncarriers, those who were heterozygous and homozygous for the variant they isolated had a 45% and 140% increased risk of type 2 diabetes, respectively, “which is a very substantial risk,” Stefansson said. Click here to see the results table.Individuals with the variant also tend to be leaner than those without it, he noted. “So basically anyone can eat themselves into type 2 diabetes, but it looks as though people who have this variant don’t need to eat as much or be as obese to become diabetics as people without the variant.” Those with this gene variant were also somewhat younger, so appear to get the disease earlier than those without it, Stefansson added. Their discovery will “definitely” lead to the development of a diagnostic test, he said. “This would offer people the opportunity, in the face of knowing that they have this risk, to modify their lifestyle to decrease the possibility that the risk will turn into the disease.” It may also allow development of new therapeutics, he added. The protein produced by this disease gene is known to be part of a signal transduction pathway that influences glucagon, a hormone that antagonizes the function of insulin, he noted. “So it influences the production of a protein that participates in glucose homeostasis; and you can say that diabetes is what happens when glucose homeostasis is interrupted.” (Source:Grant SFA, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) confers risk of type 2 diabetes. Nat Genet 2006; DOI: 10.1038/ng1732. Available at: http://www.nature.com/ng. The Heart: February 2006.)