Researchers identify genes linked to diabetes
An aid in search for treatments
Scientists announced yesterday the discovery of important genetic clues to diabetes, opening a new chapter in the study of the fast-growing disease.
An international team studying type 2 diabetes, which affects about 20 million Americans, identified two genes as culprits in the disease, and pointed to several others as potentially involved.
The results, published online yesterday by the journal Nature, will help in the search for treatments. But they are also significant because they are a striking confirmation of the power of a new kind of genetic study. This technique, which involves rapidly scanning large amounts of DNA from a large number of patients, is also being used by three other teams to identify more diabetes-related genes, and results from all the studies are expected to be announced in the coming months.
After decades of frustratingly slow progress, in which only a handful of genes have been definitively identified, researchers said the new report shows that scientists stand on the brink of identifying many important genes involved with the most common form of diabetes. This will allow them to understand more about basic biological causes of the disease -- which remain largely a mystery despite intense study.
"I think it is a phenomenal report," said Dr. Jose C. Florez , a specialist in the genetics of diabetes at Massachusetts General Hospital who is involved with one of the rival teams. "It will be a landmark year, no question."
The work is the product of a new focus in genetics on understanding common diseases. Such diseases have proven difficult to study because many genes contribute to the disease but they are hard to find using traditional techniques. Now technology available only in the last year or so makes it possible to scan for these genes, using a technique known as a "high-density whole genome association study." This has led scientists to launch genetic studies of many diseases that affect many people, including bipolar disorder, coronary heart disease, and rheumatoid arthritis.
The results announced yesterday are among the first from such a study, and they are the first for type 2 diabetes. Diabetics have trouble controlling the level of sugar in their blood, leading to a host of complications including heart disease, stroke, and blindness. Genetics plays an important role in the disease, but so do environmental influences including diet and exercise .
The research team, working in laboratories in Canada, Britain, and France, began by scanning the DNA of about 700 diabetes patients and 700 healthy patients, according to Dr. Constantin Polychronakos , a member of the team who is a professor of pediatrics and human genetics at McGill University Health Centre in Montreal. New chips that can scan large amounts of DNA enabled this step. Technicians load a patient sample into a tiny well on the chip, and the chip reads the DNA code at hundreds of thousands of locations at once and sends the results to a computer. The computer then generates a long list of genetic differences between diabetics and healthy people.
However, the initial list typically contains false positives -- genetic differences between the sick and healthy patients that show up by chance. So the team selected the 60 most striking genetic differences, and looked to see whether they were associated with the disease in a different, larger population of healthy and diabetic patients, Polychronakos said. This generated the results announced yesterday.
One of the genes the team turned up had already been linked to type 2 diabetes. Another gene is active only in the cells that make insulin, and is known to be involved in helping the cell process zinc, which plays a crucial role in insulin production. A third gene is a mystery. And the test pointed to an association with two other areas of the genome that have several genes, including some involved in the cells that make insulin.
Three other teams are preparing to announce results from similar searches for genes involved in diabetes, according to Dr. David Altshuler , a scientist at Mass. General, Harvard Medical School, and the Broad Institute of MIT and Harvard. Altshuler, who is involved in an independent study known as the Diabetes Genetics Initiative, said that the results from all four independent studies could be combined to generate an even clearer picture of the genetics underlying the disease.
On Friday, the diabetes initiative posted initial results from scans of 1,500 diabetics and 1,500 healthy patients. The data lists the association of genes with type 2 diabetes, but also with a range of other related risk factors, such as obesity. A full peer-reviewed report, including the follow-up work needed to verify the associations, will be published soon, Altshuler said. The initiative is made up of the Broad Institute,
One of the most important applications for the research, scientists said, could be to help break down type 2 diabetes into subcategories, each with its own genetic signature. It would then be possible to test various treatments -- from diet changes to drugs -- on the different kinds of diabetes, according to Dr. David M. Nathan , director of the diabetes center at Mass. General. However, Nathan cautioned, patients should not take zinc supplements or otherwise change their medications based on the new work.
Polychronakos said his team would have more results as well. Thousands of potentially linked genes identified in the first phase of the study need to be checked in a second group of people. The vast majority of the genes will probably not turn out to be linked, he said, but many will.
"This is a big breakthrough," he said, "but it is only the tip of the iceberg."
Gareth Cook can be reached at cook@globe.com. 
