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Senior Citizen Health & Medicine
Researchers Funded to Narrow Search for Genes
Causing Diabetes
Scientific group has already found 100 genes
influencing diabetes, metabolic diseases
 Dec. 12, 2007 – If scientist knew the exact gene
that caused high blood sugar in diabetics, it might then be possible to
alter that gene to control the glucose level and stop the disease.
Scientists at Southwest Foundation for Biomedical Research (SFBR) expect
to make big leaps in their understanding of genetic influences on
diabetes, thanks to a new $1.7 million grant awarded to Dr. Joanne
Curran, the grant’s principal investigator.
The grant from the National Institute for Diabetes
and Digestive and Kidney Diseases will allow Dr. Curran and her
colleagues to conduct a more detailed investigation on 100 genes that
previous SFBR studies have shown to play a role in various risk factors
for diabetes and other metabolic diseases.
She will now look closely at DNA variations within
the genes themselves to see how those changes affect the genes’ output,
and ultimately, how these genes exert their influence on such things as
blood glucose and insulin levels and body fat.
“We’re looking for functional changes within the
DNA sequence of these particular genes that are causing certain
individuals to have these risk factors for diabetes,” Curran said. “Our
previous work has uncovered genes that are influencing fasting glucose
levels, body mass index, and other health traits related to diabetes
risk. So now we want to find out how these genes vary among individuals
and which DNA variations within the genes themselves impact their
function and their resulting influence on human health.
 “Then maybe we can find a way to target a
particular gene and manipulate its function so that it doesn’t result in
high blood glucose levels, for example.”
The need for new methods of preventing and treating
diabetes is critical, as rates of type 2 diabetes, often called
adult-onset diabetes, continue to climb in the United States and other
first-world countries, particularly as obesity rates have reached
epidemic levels. It disproportionately affects the growing Hispanic
population, where the prevalence of type 2 diabetes is two to three
times higher than in non-Hispanic whites.
Obesity often precedes the
onset of type 2 diabetes, which can make people more susceptible to a
host of other health problems, including cardiovascular disease, kidney
disease, and blindness. Type 2 diabetes accounts for more than 90
percent of diabetes worldwide, with scientists estimating that there
will be 220 million cases worldwide by 2010.
“Right now, the best prevention we have for
diabetes is lifestyle change,” said Curran.
“But what if you have a
genetic predisposition that’s causing your high levels of blood glucose?
Then lifestyle changes alone may not help you. That’s why we need to
find the genes involved and the DNA variations that affect those genes’
function. That will give pharmaceutical companies the information they
need to develop new medications to fight this growing health problem.”
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About Diabetes
Also called: Adult onset diabetes, Non-insulin
dependent diabetes, “Sugar”
Diabetes is a disease in which your blood glucose,
or sugar, levels are too high. Glucose comes from the foods you eat.
Insulin is a hormone that helps the glucose get into your cells to give
them energy.
With Type 1 diabetes, your body does not make insulin. With
Type 2 diabetes, the more common type, your body does not make or use
insulin well. Without enough insulin, the glucose stays in your blood.
Over time, having too much glucose in your blood
can damage your eyes, kidneys, and nerves. Diabetes can also cause heart
disease, stroke and even the need to remove a limb. Pregnant women can
also get diabetes, called gestational diabetes.
Symptoms of Type 2 diabetes may include fatigue,
thirst, weight loss, blurred vision and frequent urination. Some people
have no symptoms.
A blood test can show if you have diabetes. Exercise,
weight control and sticking to your meal plan can help control your
diabetes. You should also monitor your glucose level and take medicine
if prescribed.
National Institute of Diabetes and Digestive and
Kidney Diseases
>>…More
at MedlinePlus for Seniors
Other links:
>>
Diabetes - Introduction (Patient Education Institute) - Requires
Flash Player - Also available in
Spanish
>>
Diabetes Overview (National Institute of Diabetes and Digestive and
Kidney Diseases)
>>
Your Guide to Diabetes: Type 1 and Type 2 (National Institute of
Diabetes and Digestive and Kidney Diseases) - Also available in
Spanish
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>> The hunt for diabetes genes
SFBR geneticists have particular expertise in the
search for genes that influence common complex diseases like diabetes
and other disorders that are influenced by numerous environmental and
genetic risk factors. In September of 2007, they announced a new
research method they devised to speed up this cumbersome hunt.
That study, led by SFBR geneticist Dr. John
Blangero, and detailed in the scientific journal Nature Genetics,
utilized genetic material from blood samples from 1,240 participants in
SFBR’s ongoing San Antonio Family Heart Study. The San Antonio Family
Heart Study includes approximately 1,400 members of 40 Mexican-American
families in the San Antonio area, who are participating in a long-term
investigation of the genetic determinants of heart disease, diabetes and
obesity.
Instead of trying to sift through all 25,000 genes
in the human genome, the researchers used transcriptional profiles –
measures of the output of a person’s genes – to identify genes that are
self-regulated, or cis-regulated, meaning they harbor variations that
affect their own output.
That enabled them to rapidly narrow in on genes
that likely have a causal effect on a particular disease or disease
trait. In the Nature Genetics paper, the SFBR team described how it
discovered the VNN1 gene’s influence on the level of HDL, or “good
cholesterol,” by statistically correlating the gene expression profiles
with the variable HDL cholesterol levels in the San Antonio Family Heart
Study participants.
SFBR scientists have used that same approach to
find genes associated with other diseases, including 203 genes that
correlate with risk factors for diabetes. From that list of 203 genes,
Dr. Curran has selected the top 100 for further examination.
She will look at the 100 genes that showed the
strongest evidence of being self-regulated and the strongest
correlations with diabetes risk factors such as a high level of glucose
in the blood after a period of fasting, known as fasting glucose; other
risks determined by tests of glucose and insulin; and a high level of
fat as determined by assessment of the body mass index, the measure of
fat in relation to height and weight.
>> What makes these genes tick?
In her more detailed investigation, Curran’s group
will utilize genetic samples from 182 founder individuals in the San
Antonio Family Heart Study and search for variations in an area of the
genes known as the promoter region, a key regulatory region of the gene.
“By focusing on the promoter region, we’re likely to find functional DNA
variants within the genes, or variants that truly have a functional
consequence in the cellular system, which is our ultimate aim,” said
Curran.
She further explained, “Analyzing the founders [of
the San Antonio Family Heart Study] enables us to capture most of the
genetic variation that’s present in the population without having to
sequence everybody. These are the people who contribute most of the
genetic information to the family trees in our study. So by picking
those individuals, we really increase our chance of getting all the
genetic information we need.”
>> Impact on human health
Curran sees a two-fold benefit from identifying
genes that influence our risk for diabetes. “Knowing you have a genetic
predisposition for diabetes can be a wake-up call that you need to stay
in shape and manage your diet to try and keep your blood sugar under
control,” she said.
“But in cases where a person still exhibits those
risk factors, despite lifestyle changes, perhaps a drug targeting genes
that influence the risk factors can keep them under control.”
The researchers also will test the findings of this
study with two independent populations. One is in Wisconsin, the
Metabolic Risk Complications of Obesity Genes Study, directed by Dr.
Ahmed Kissebah, of the Medical College of Wisconsin, a co-investigator
on Curran’s study. The other is a group involved in the San Antonio
Family Gall Bladder Study, directed by SFBR geneticist Dr. Ravindranath
Duggirala, a consultant on Curran’s study.
Other co-investigators on Curran’s study include
Drs. John Blangero and Jac Charlesworth.
Southwest Foundation for Biomedical Research is one
of the leading independent biomedical research institutions in the
United States, dedicated to advancing human health through innovative
biomedical research. It is recognized within scientific and academic
communities worldwide for the quality of its basic research into the
nature, causes, preventions, and treatments for disease. SFBR’s staff of
more than 75 doctoral-level scientists conducts nearly 200 major
research projects, with marked success in the areas of genetics,
neonatal development, metabolic disorders and infectious diseases.
For more information about diabetes, visit the
American Diabetes Association Web site
http://www.diabetes.org or call 1-800-DIABETES (1-800-342-2383).
American Diabetes Association (ADA)
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