In a scientific paper published today a team
of scientists from deCODE genetics (Nasdaq:DCGN) and colleagues report
the discovery of a variant in a gene on chromosome 10 that represents
the most significant genetic risk factor for type 2 diabetes (T2D)
found to date. More than one third of individuals in the populations
studied carry one copy of the at-risk variant and are at an
approximately 45% increased risk of the disease compared to controls;
7% carry two copies and are at a 141% greater risk. The original
finding was made in Iceland and was subsequently confirmed in studies
in Denmark and the United States. The paper is published today in the
online edition of Nature Genetics at www.nature.com/ng, and will appear in the journal's February print edition.
"This is a milestone in human genetics. A common gene variant
conferring elevated risk of T2D has been earnestly sought by the
genetics community for many years. We have found such a variant, which
we estimate accounts for about 20% of T2D cases. This discovery sheds
new light on the biological causes of the disease. Importantly,
virtually all of this risk can be captured by looking at a
single-letter change in DNA - ideal for the development of a
genetic test for assessing individual risk and developing more
personalized and effective prevention strategies. This is also an
exciting starting point for the discovery of new drugs, and we are
actively pursuing the development of both diagnostic and therapeutic
products to better prevent and treat T2D," said Kari Stefansson, CEO of
deCODE and senior author on the study.
The variant is located in a gene encoding a protein called
transcription factor 7-like 2 (TCF7L2). deCODE isolated the gene by
following up on the results of a population-based, genome-wide linkage
scan in Iceland that identified a promising region on chromosome 10.
The deCODE team genotyped 228 microsatellite markers - polymorphic
signposts along the genome - in this region in a total of more
than 2000 patients and controls. Analysis of the frequency of different
alleles, or versions, of these markers pinpointed a version of one
marker within the gene encoding TCF7L2 that is approximately 1.5 times
more common in patients than in controls. This corresponds to a 50%
increase in risk of T2D per copy carried (there are two copies of each
chromosome in every cell).
This finding was replicated in
Danish and U.S. cohorts, where the at-risk version of the marker was
found to confer an increased risk of 41% and 85%, respectively, per
copy carried. For all of the cohorts combined, the at-risk allele
confers an increase in risk of approximately 45% for those carrying one
copy, and a 141% increase in risk for individuals carrying two copies.
Utilizing data from the HapMap project, a SNP was found that correlates
nearly perfectly with the at-risk microsatellite.
Diabetes: A major public health problem
Diabetes
affects nearly 200 million people worldwide and an estimated 21 million
in the United States - 7% of the population. The vast majority of
diabetes patients have type 2 diabetes, a condition where the body does
not produce enough insulin and/or the cells in the body do not properly
use insulin. In the United States, the direct medical cost associated
with diabetes is nearly $100 billion per year. The incidence of type 2
diabetes is increasing rapidly in the industrialized world, in part due
to the increase in obesity, one of the major risk factors for
developing the disease.
About deCODE
deCODE genetics (Nasdaq:DCGN) is a
biopharmaceutical company applying its discoveries in human genetics to
the development of drugs for common diseases. deCODE is a global leader
in gene discovery " our population approach and resources have
enabled us to isolate key genes contributing to major public health
challenges from cardiovascular disease to cancer, genes that are
providing us with drug targets rooted in the basic biology of disease.
deCODE is also leveraging its expertise in human genetics and
integrated drug discovery and development capabilities to offer
innovative products and services in DNA-based diagnostics,
bioinformatics, genotyping, structural biology, drug discovery and
clinical development. deCODE is delivering on the promise of the new
genetics.SM Visit us on the web at www.decode.com.
