Post by anodyne on Jan 15, 2006 17:33:20 GMT -5
Scientists Discover Gene That Confers Sizable Risk of Diabetes
By NICHOLAS WADE
Published: January 15, 2006
Scientists have discovered a variant gene that confers a sizable extra risk of Type 2 diabetes and that is carried by more than a third of the American population.
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The finding is being reported on Monday in the journal Nature Genetics by researchers at Decode Genetics. The company specializes in finding the genetic roots of human diseases by studying the Icelandic population. Decode Genetics first found the genetic variant in Icelanders and has now confirmed the finding in a Danish and an American population.
An immediate practical consequence of the discovery, Decode's chief executive, Kari Stefansson, said, will be a diagnostic test to identify people who carry the variant gene. If they know of their extra risk, he said, they will have an added incentive to stay thin and exercise.
Diabetes, which allows excess sugar to build up in the blood, leading to damage throughout the body, has reached significant proportions in many parts of the United States. It is a leading cause of blindness and loss of limbs. Type 2 diabetes, the predominant form, is typically diagnosed in adults and adolescents, though it is creeping into younger age groups.
The 38 percent of Americans who have inherited one copy of the variant gene have a 45 percent greater risk of Type 2 than do unaffected members of the population, and the 7 percent who carry two copies are 141 percent more likely to develop the disease, according to the Decode researchers, who were led by Struan F. A. Grant.
What scientists call the "population-attributable risk" of the new variant is 21 percent, which means that if all the variant genes were removed, so would 21 percent of diabetes cases.
The finding is "a beautiful piece of work and as convincing as any initial publication could be," said David Altshuler, a medical geneticist at the Massachusetts General Hospital, who has in the past taken issue with certain aspects of Decode's claims.
"In terms of the epidemiological risk of diabetes, this is by far the biggest finding to date," he said, just after hearing a lecture on the finding by Decode's chief statistician, Augustine Kong. Diabetes is thought to be caused by a variety of different genes, each conferring a risk for the disease. Because most of the variants exert a minor effect, they are hard to detect, and many claims to have found diabetes-causing genes have turned out to be unfounded.
"This has turned out to be the disease that has been the most difficult for geneticists to crack, probably because of the large environmental contribution," said Dr. Stefansson, the Decode chief executive.
The new variant identified by Decode is of a somewhat obscure gene that had not been suspected of having any involvement in diabetes. The gene, designated TCF7L2, is one that controls the activity of other genes. Its role may include setting the level of a hormone that acts along with insulin to control blood sugar levels.
Discovery of the TCF7L2 gene could be therapeutically helpful, Dr. Stefansson said, because it identified a major biochemical pathway through which the disease developed. Any of the genes and proteins that govern the pathway is a potential target for new drugs.
Dr. Altshuler, of Massachusetts General, agreed. "Being directed down that pathway is very helpful," he said, though he added that the process of developing better treatments might take a decade or two.
While Type 2 diabetes is more common in African-Americans, Latinos, American Indians and Asian-Americans, Dr. Stefansson said more studies were needed to see whether there were significant differences in the variant gene's distribution among races.
He said he could not yet say if the genetic variant was more common in African-Americans and so might explain their greater burden of Type 2 diabetes. But he noted that the variant was ancient, having arisen before the dispersal of modern humans from Africa thousands of years ago, and was found in all populations.
By NICHOLAS WADE
Published: January 15, 2006
Scientists have discovered a variant gene that confers a sizable extra risk of Type 2 diabetes and that is carried by more than a third of the American population.
Skip to next paragraph
The finding is being reported on Monday in the journal Nature Genetics by researchers at Decode Genetics. The company specializes in finding the genetic roots of human diseases by studying the Icelandic population. Decode Genetics first found the genetic variant in Icelanders and has now confirmed the finding in a Danish and an American population.
An immediate practical consequence of the discovery, Decode's chief executive, Kari Stefansson, said, will be a diagnostic test to identify people who carry the variant gene. If they know of their extra risk, he said, they will have an added incentive to stay thin and exercise.
Diabetes, which allows excess sugar to build up in the blood, leading to damage throughout the body, has reached significant proportions in many parts of the United States. It is a leading cause of blindness and loss of limbs. Type 2 diabetes, the predominant form, is typically diagnosed in adults and adolescents, though it is creeping into younger age groups.
The 38 percent of Americans who have inherited one copy of the variant gene have a 45 percent greater risk of Type 2 than do unaffected members of the population, and the 7 percent who carry two copies are 141 percent more likely to develop the disease, according to the Decode researchers, who were led by Struan F. A. Grant.
What scientists call the "population-attributable risk" of the new variant is 21 percent, which means that if all the variant genes were removed, so would 21 percent of diabetes cases.
The finding is "a beautiful piece of work and as convincing as any initial publication could be," said David Altshuler, a medical geneticist at the Massachusetts General Hospital, who has in the past taken issue with certain aspects of Decode's claims.
"In terms of the epidemiological risk of diabetes, this is by far the biggest finding to date," he said, just after hearing a lecture on the finding by Decode's chief statistician, Augustine Kong. Diabetes is thought to be caused by a variety of different genes, each conferring a risk for the disease. Because most of the variants exert a minor effect, they are hard to detect, and many claims to have found diabetes-causing genes have turned out to be unfounded.
"This has turned out to be the disease that has been the most difficult for geneticists to crack, probably because of the large environmental contribution," said Dr. Stefansson, the Decode chief executive.
The new variant identified by Decode is of a somewhat obscure gene that had not been suspected of having any involvement in diabetes. The gene, designated TCF7L2, is one that controls the activity of other genes. Its role may include setting the level of a hormone that acts along with insulin to control blood sugar levels.
Discovery of the TCF7L2 gene could be therapeutically helpful, Dr. Stefansson said, because it identified a major biochemical pathway through which the disease developed. Any of the genes and proteins that govern the pathway is a potential target for new drugs.
Dr. Altshuler, of Massachusetts General, agreed. "Being directed down that pathway is very helpful," he said, though he added that the process of developing better treatments might take a decade or two.
While Type 2 diabetes is more common in African-Americans, Latinos, American Indians and Asian-Americans, Dr. Stefansson said more studies were needed to see whether there were significant differences in the variant gene's distribution among races.
He said he could not yet say if the genetic variant was more common in African-Americans and so might explain their greater burden of Type 2 diabetes. But he noted that the variant was ancient, having arisen before the dispersal of modern humans from Africa thousands of years ago, and was found in all populations.