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deCODE Genetics, in Collaboration with Academic Colleagues and Illumina, Discovers Two Rare Variants that Affect the Risk of Gout and Serum Uric Acid Levels
Date:10/9/2011

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 alcohol-induced flushing.

Also, at a previously reported locus on chromosome 1, the researchers discovered another novel low frequency variant associ
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