Pooled DNA technique identifies variances that could indicate
susceptibility to end-stage renal disease
PHOENIX, Ariz. -- Dec. 16, 2009 -- Researchers using a DNA analysis
tool developed by the Translational Genomics Research Institute
(TGen) and UCLA have identified genetic markers that could help
treat chronic kidney disease among diabetics.
Study results, published in the December edition of Diabetic
Medicine, show it is possible to identify biomarkers associated
with end-stage renal disease (ESRD) from the pooled DNA of more
than 1,000 diabetics. Specifically, TGen researchers identified
genes that could potentially contribute to ESRD among those with
Type 1 Diabetes.
ESRD almost always follows chronic kidney failure and although
treatable with dialysis or transplantation, mortality rates remain
high. While diabetic kidney disease is one of the most common
complications of diabetes, it is currently not possible to
determine who is at risk for ESRD.
"Identification of specific DNA variants may enhance our
understanding of genetic risk factors for renal disease and may
provide diagnostic value in determining which patients are at
greatest risk of developing ESRD," said Dr. Johanna DiStefano,
Director of TGen's Diabetes, Cardiovascular & Metabolic
Diseases Division and the paper's senior author.
The need to rapidly identify individuals with a predisposition to
ESRD and to discover new drugs to prevent and treat this
devastating condition is becoming critical, as the average onset of
this disease affects ever-younger populations. Although Type 1
diabetes is distinctly different from Type 2 diabetes, the
development of kidney disease is similar in individuals with either
form. Researchers expect the current findings to impact individuals
with both forms of the disease.
Nearly 23 percent of Americans diagnosed with ESRD die within the
first year. And the annual cost for the nearly 400,000 people who
require blood dialysis or kidney transplants is more than $16
billion.
TGen researchers tested the pooled genomic DNA from more than 500
cases of those with ESRD and compared that to more than 500
patients who had Type I diabetes for at least 20 years with no sign
of ESRD. Scientists performed a whole genome association scan to
look for single nucleotide polymorphisms (SNPs), which are the
individual letters of DNA that vary among individuals. They sought
SNPs that indicate a susceptibility to ESRD.
Experiments identified at least eight locations along the nearly
3-billion-base human genome that are ripe for further investigation
of their ties to ESRD, according to the paper, Genome-wide SNP
genotyping study using pooled DNA to identify candidate markers
mediating susceptibility to end-stage renal disease attributed to
Type 1 diabetes.
The study found at least six markers that may be associated with
Type 1 diabetes, a lifelong disease that occurs when the pancreas
does not produce enough insulin to properly control blood-sugar
levels. There currently is no way to prevent Type 1, which is
caused by autoimmune, genetic or environmental factors.
The study found two markers that may be associated with Type 2
diabetes, the most common form of diabetes. Type 2 develops when
the body fails to produce enough insulin, which helps turn glucose
from the sugars and starches we eat into energy. The failure to
process glucose starves cells of energy and over time can damage
the eyes, nerves, heart or kidneys. Type 2 diabetes can be
prevented or treated with proper diet and exercise.
Using a similar pooled DNA analysis, TGen researchers, working with
collaborators at the University of California Los Angeles, last
year developed a way to identify an individual's DNA from among a
mixture of DNA of hundreds or even thousands of individuals.
"This technique will increasingly be used in identifying the
genetic origins of many Types of disease,'' predicted Dr. David
Craig, Associate Director of TGen's Neurogenomics Division, who
co-developed the technique and was lead author of the current
study.
Diabetic nephropathy, or kidney disease, is the most common cause
of ESRD. It occurs when chronic kidney failure has progressed to
the point when either dialysis or kidney transplants are required
to prevent blood poisoning.
Nearly 24 million Americans, about 8 percent, have diabetes,
according to the American Diabetes Association, which lists the
disease as the nation's seventh leading cause of death.
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About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]