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Gene clue in diabetes research

17 March 2004
By BioNews
Appeared in BioNews 250

Two new studies have identified a link between type 2 diabetes, also known as adult-onset diabetes, and variations in a gene involved in regulating the body's glucose levels. One study, carried out by Finnish and US researchers, looked at 793 Finnish adults with the disease and compared them to 413 non-diabetic controls. The other team, based at the Washington University School of Medicine, US, studied 275 Ashkenazi Jewish Israeli adults with type 2 diabetes, and 342 healthy controls. Both studies, published in the journal Diabetes, found that alterations in a gene called HNF4A appeared to increase the risk of developing the illness.

Type 2 diabetes usually affects people over the age of 40. It is more common in overweight, inactive people, and those with a family history of the disease, which suggests that genetic factors are also involved. People with diabetes cannot regulate their blood sugar levels properly, either because their pancreas is not making enough of the hormone insulin, or because the body becomes resistant to its effects.

The HNF4A gene makes a protein that controls the activity of other genes, including those involved in the release of insulin into the bloodstream. A team lead by researchers at three US institutes and the National Public Health Institute in Helsinki, Finland, identified several different variations in the HNF4A gene in Finnish patients with type 2 diabetes. One of these appeared to increase the risk of the disease by about a third. But, says lead author Francis Collins of the US National Human Genome Research Institute, the variation 'isn't going to cause diabetes unless you have it in combination with other yet-to-be identified genetic susceptibility factors' together with non-genetic factors such as 'obesity and lack of physical exercise'. Collins also said that while there are no immediate implications, it might be possible one day to screen for genetic susceptibility to the illness, adding: 'It would be nice to know when you are 21 so you could do something to prevent it'.

The other study also found a link between type 2 diabetes and a block of four variations in the same region of the HNF4A gene, in Ashkenazi Jewish adults with the disease. Team leader Dr M Alan Permutt said that the gene variant identified in the study probably affected the amount of protein produced by HNF4A. A previous study published in Science earlier this year had already suggested that this gene might be involved in diabetes, after studying its role in the body. 'The work builds on a solid foundation of advances in basic cell biology, studies in human populations and new gene-scanning technologies', said Catherine McKeon of the US National Institute of Diabetes and Digestive and Kidney Diseases, which funded the studies. The researchers are now planning to see if the HNF4A variants are linked to type 2 diabetes in other populations.

SOURCES & REFERENCES
Changes in gene may make people prone to diabetes
Reuters |  11 March 2004
Gene variants may increase susceptibility to type 2 diabetes
ScienceDaily |  12 March 2004
Researchers find potential gene link to diabetes
Newsday.com |  12 March 2004
Two research teams find genetic variations connected to diabetes
The Kansas City Star |  13 April 2004
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