deCODE Genetics, in Collaboration with Academic Colleagues and Illumina, Discovers Two Rare Variants that Affect the Risk of Gout and Serum Uric Acid Levels
REYKJAVIK, Iceland, October 9, 2011 /PRNewswire/ –
Scientists at deCODE Genetics and academic collaborators from Iceland,
Norway, Denmark, the Netherlands and the USA today report the discovery of
low frequency variants in the human genome that associate with risk of gout,
a common inflammatory arthritis, and serum uric acid levels. The study was
done in collaboration with Illumina, Inc., and is published today in the
online edition of Nature Genetics.
Using Illumina sequencing technology, deCODE scientists determined the
sequences of the entire genomes of 457 Icelanders, and identified 16 million
single nucleotide polymorphisms (SNPs). Through a combination of SNP
genotyping and computational techniques utilizing the extensive Icelandic
genealogy, they were able to propagate those 16 million variants into over
40,000 Icelanders, including over 1,200 patients with gout and over 22,000
individuals for whom serum uric acid measurements were available.
The researchers observed a sequence variant in a previously unidentified
gout susceptibility gene located on chromosome 19 that has a large effect on
serum uric acid levels and gout. The sequence variant is a mis-sense
mutation that causes an increase in the level of uric acid by 0.04 mmol/L
and a three-fold increase in the risk of gout. Close to 4% of individuals in
the overall Icelandic population carry this variant, and ~0.2% of the
individuals assessed by academic collaborators in Norway, Denmark, The
Netherlands and the United States.
The variant encodes an amino acid change in ALDH16A1, a member of the
aldehyde dehydrogenase (ALDH) superfamily, and could motivate further
biological studies of this pathway. Other members of the ALDH superfamily
have been associated with other clinical phenotypes including
Also, at a previously reported locus on chromosome 1, the researchers
discovered another novel low frequency variant associating with serum uric
acid level and gout. The variant decreases the risk of gout by 50%, and the
level of uric acid by 0.05 mmol/L. Approximately 3% of the Icelandic
population carry this variant and 1.5% of the European subjects.
For both loci the effect on risk of gout is significantly higher among
men than women, but the effect on serum uric acid levels is the same in both
“This study underscores the importance of whole genome sequencing of
well-phenotyped populations. We are pleased that the clinical and genetic
resource that deCODE has built enables us to make such discoveries,” said
Kari Stefansson, deCODE’s CEO and senior author of the study.
“We are committed to turning discoveries such as this, as well as our
recent findings in ovarian cancer and sick sinus syndrome, and our future
discoveries, into real benefit for patients,” Dr. Stefansson continued.
Gout is a common inflammatory arthritis caused by urate crystal
formation resulting from a high concentration of uric acid in the blood,
which is in turn caused by an imbalance in the dietary intake of purines and
in the synthesis an excretion of urate. The incidence of gout increases with
age and is three times higher in men than in women.
Headquartered in Reykjavik, Iceland, deCODE genetics is a global leader
in analyzing and understanding the human genome. Using its unique expertise
and population resources, deCODE has discovered genetic risk factors for
dozens of common diseases ranging from cardiovascular disease to cancer.
In order to most rapidly realize the value of genetics for human health,
deCODE is currently partnering with life sciences companies to accelerate
their target discovery, validation, and prioritization efforts, yielding
improved patient stratification for clinical trials and essential companion
diagnostics. In addition, through its CLIA- and CAP-certified laboratory,
deCODE offers DNA-based tests for gauging risk and empowering prevention of
common diseases. deCODE also licenses its tests, intellectual property, and
analytical tools to partner organizations. deCODE’s corporate information
can be found at http://www.decode.com with information about our genetic
testing services at http://www.decodehealth.com and
Contact: Gisli Arnason +354-570-1825 email@example.com
SOURCE deCODE genetics