Gene variants may increase susceptibility to type 2 diabetes

BETHESDA, MD, Thursday, March 11, 2004 -- International research teams studying two distinct populations have found variants in a gene that may predispose people to type 2 diabetes, the most common form of the disease. The researchers, who collaborated extensively in their work, report their findings in companion articles in the April issue of Diabetes.

"This is an outstanding example of how scientists are using the tools of modern biology to understand the causes of our nation's most common--and most devastating--diseases," said Dr. Elias A. Zerhouni, Director of the National Institutes of Health (NIH). "As researchers continue to build upon the foundation laid by the Human Genome Project, we can expect even swifter progress in our effort to understand, treat and eventually prevent many complex conditions such as diabetes, heart disease and mental illness."

Homing in on a wide stretch of chromosome 20 flagged by earlier studies as a likely location for a type 2 diabetes susceptibility gene, the teams identified four genetic variants, called single nucleotide polymorphisms (SNPs), which are strongly associated with type 2 diabetes in Finnish and Ashkenazi Jewish populations.

All four SNPs cluster in the regulatory region of a single gene, hepatocyte nuclear factor 4 alpha (HNF4A), a transcription factor that acts as a "master switch" regulating the expression of hundreds of other genes. HNF4A turns genes on and off in many tissues, including the liver and pancreas. In the beta cells of the pancreas, it influences the secretion of insulin in response to glucose.

"It's a nice coalescence of findings," said Dr. Francis S. Collins, Director of the National Human Genome Research Institute (NHGRI) and senior author of the article describing the Finnish study results. "What we found is a common variation in this gene. If you have this variation, it appears to raise your risk of type 2 diabetes about 30 percent. The variation isn

Contact: Geoff Spencer
NIH/National Human Genome Research Institute

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