Scientists
Discover Gene That Confers Sizable Risk of Diabetes
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.
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.