Scientists identify new genes linked to diabetes

WASHINGTON Thu Apr 26, 2007 4:03pm EDT

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WASHINGTON (Reuters) - The most thorough probe to date of the genetic underpinnings of the most common form of diabetes has identified a new batch of genes that increases risk for a disease affecting 200 million people globally.

The findings by four international teams of researchers, published on Thursday in the journals Science and Nature Genetics, provided great insight into the role played by genes in a disease also tremendously influenced by behavior -- eating too much and exercising too little.

The scientists hope the findings can help guide development of new drugs to treat type 2 diabetes, previously known as adult-onset diabetes, and genetic tests to determine a person's predisposition for developing it.

Despite its growing global prevalence, the disease's underlying causes have been only minimally understood, restricting treatment and prevention efforts.

The scientists scoured the entire human genome -- more than 22,000 known genes -- of about 50,000 people in several countries with and without the disease.

They identified at least eight genes that are clear diabetes risk factors -- including three previously unknown ones -- and several other likely risk factors that merit further attention. All are common in the general population.

"I think we've made a quantum leap here in terms of our understanding of the genetic variants that contribute as risk factors to type 2 diabetes," Michael Boehnke of the University of Michigan, who led one of the teams, said in a telephone interview.

In diabetics, one's body fails to produce or properly use insulin, a hormone necessary to convert sugar, starches and other food into energy. It is a leading cause of heart disease, stroke, blindness, kidney failure and amputations.

"TOTALLY SURPRISING"

The role of the three new genes is unclear. Two may be linked to the development, function and regeneration of certain insulin-producing cells in the pancreas.

"The genes that have been found here are, without exception, totally surprising," David Altshuler of the Broad Institute of Harvard University and the Massachusetts Institute of Technology, who led another team, said in an interview.

Altshuler said at the beginning of the work researchers listed every gene any of them could imagine had a connection to diabetes. None of them panned out.

Lifestyle factors such as obesity, poor diet and lack of exercise play a major role in diabetes. Its rising prevalence tracks an increase in obesity in many parts of the world.

Scientists long have known heredity also is a major factor in determining risk of developing it. Researchers only recently began to find specific genes that raise or lower this risk.

"We have the possibility of getting a very, very powerful predictive test that measures your risk of developing type 2 diabetes," said Dr. Kari Stefansson, president and CEO of Icelandic company deCODE genetics Inc., which led another team.

Incidence of type 2 diabetes -- as opposed to type 1, usually diagnosed in children and young adults, and gestational diabetes affecting some pregnant women -- has soared in the United States and other developed nations in the past three decades.

Altshuler said genes alone cannot account for this big increase, which certainly is driven by lifestyle issues. But he estimated that in a given population, risk for diabetes is probably half genetic and half behavioral.

Type 2 diabetes most commonly appears after age 40 in overweight, sedentary individuals, but a growing number of younger people and sometimes children are developing it as obesity becomes more prevalent.

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