Gene variants may increase susceptibility to type ...( 't going to cause diabetes unless you h...)

Translating the discovery into a treatment that benefits people with diabetes or those at risk is still years away. "We need to learn much more about this gene and how to modulate its function," Dr. Collins cautioned.

The Finland-United States Investigation of NIDDM Genetics (FUSION) study is led by Dr. Michael Boehnke at the University of Michigan, Drs. Jaakko Tuomilehto and Timo T. Valle at the National Public Health Institute in Helsinki, Dr. Richard N. Bergman at the University of Southern California, and Dr. Collins at NHGRI. Drs. Kaisa Silander and Karen L. Mohlke, both of NHGRI, were co-lead authors on the study. The team examined polymorphisms in 793 Finnish adults diagnosed with typical type 2 diabetes (formerly known as adult-onset or non-insulin dependent diabetes--NIDDM) and 413 non-diabetic controls. The researchers identified a total of 10 SNPs within and near the HNF4A gene that are associated with type 2 diabetes in the Finnish population. The most significant results were found in a region of DNA (called the "promoter") that regulates the gene's expression in the insulin-secreting cells of the pancreas. Individuals who inherited the risk variant tended to have higher levels of blood glucose at fasting and 2 hours after a glucose challenge.

The other international team of researchers, led by Dr. M. Alan Permutt of the Washington University School of Medicine in St. Louis, studied 100 SNPs in 275 Ashkenazi Jewish adults in Israel with type 2 diabetes and 342 non-diabetic controls. They found diabetes-related associations for SNPs in the same region of HNF4A.

"We believe these four variants are marking a regulatory region that determines the level of expression of HNF4A," Dr. Permutt said. "
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
11-Mar-2004