Gene variants may increase susceptibility to type ...( We're now looking to see if this region...)

An NIH-funded study in the Feb. 27, 2004, issue of Science suggests how polymorphisms in the HNF4A promoter might confer susceptibility to type 2 diabetes. In that work, Dr. Richard A. Young of the Whitehead Institute for Biomedical Research in Boston and coworkers examined the genes regulated by several HNF transcription factors. They found HNF4A to be a highly active transcription factor, regulating a surprising number of beta cell and liver cell genes in humans. A misstep in the binding site for other transcription factors in the HNF4A promoter, they conclude, could result in "misregulation of HNF4A expression and thus its downstream targets, leading to beta cell malfunction and diabetes."

"The observations made by these groups mark a real leap forward in our understanding of the genetics of diabetes and may provide a blueprint for finding genes in other complex diseases," said Dr. Catherine McKeon of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which funded the three studies. "The work builds on a solid foundation of advances in basic cell biology, studies in human populations, and new gene-scanning technologies."

Other groups still need to confirm their results, Drs. Collins and Permutt stress. In fact, scientists are already looking for the variants in other populations. "We've e-mailed our findings in precise detail to scientists in the International Type 2 Diabetes Linkage Analysis Consortium," said Dr. Boehnke, who co-leads the NIDDK-funded consortium, a group of scientists around the world who are mapping type 2 diabetes susceptibility genes. "This approach will substantially increase the speed with which we see our results confirmed or contradicted," he added. Other studies will see if people with the risk variants have signs of beta cell impairment and will look at HNF4A's function in animals.
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
11-Mar-2004