A couple of genes have recently been linked with type 2 diabetes. These
results are the first fruit of a new method of genetic screening,
which may greatly accelerate research in this area. There are
currently many mysteries to diabetes, and this research should be a
big step in understanding more about the biology of the disease – how
do genes interact with the environment (i.e. diet and exercise) to
produce type 2 diabetes? What sort of clinical application this
information will have is hard to tell.
It can be tough to know how relevant the latest scientific advance can
be for patients. Some advances go nowhere and others go somewhere;
some go somewhere fast and others almost imperceptibly slowly. We
think that it is great to see advances here, but at this point, they
are not so much "page one" news. However, continued research in the
area could be used to break down type 2 diabetes into genetic
subcategories. Specific treatment paradigms could be tested on each
subcategory, presumably with the goal of matching each subtype of type
2 diabetes with an optimum treatment plan. Down the road – far down
the road – this understanding may reduce fumbling with drug options to
find effective combinations in a given patient.
These results were published in the journal Nature on February 11,
along with a description of this new gene-screening technique: a
"high-density whole genome association study". This technology has
only recently become available and makes it easier to study the
genetics of diseases like diabetes, which are effected by many, many
genes. The study method involves tiny chips loaded with DNA from
diabetic subjects and non-diabetic subjects. A computer reads these
chips and then identifies genetic differences between the two groups.
Frequent false positives require re-testing of the most interesting
differences in different, larger populations – some genetic
differences are confirmed and others are thrown out. At the moment,
four organizations are using this technique to link genes to type 2
diabetes, and collectively, their results, expected to be announced in
the next few months, will paint a clearer picture of type 2 diabetes.
Read the Boston Globe article below:
Researchers identify genes linked to diabetes
An aid in search for treatments
By Gareth Cook, Globe Staff | February 12, 2007
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, Novartis, and Lund University in
Sweden.
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."
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