Common SNP in sequence of human genome conferring risk of vascular diseases discovered

DeCODE Genetics IncJul 12 2010

Points to Novel Pathway for Drug Discovery, Will be Incorporated Into Tests to Improve Screening and Early Detection of Abdominal Aortic Aneurysm, Heart Attack and PAD

Scientists at deCODE genetics and academic colleagues from the Netherlands and twelve other countries across Europe and North America today report the discovery of a common single-letter variation (SNP) in the sequence of the human genome conferring risk of a range of vascular diseases. The SNP confers risk of abdominal aortic aneurysm (AAA), early-onset heart attack, peripheral artery disease (PAD), and pulmonary embolism, independent of other known risk factors. It will be integrated into deCODE's DNA-based tests to improve the assessment of individual risk and the targeting of screening and prevention strategies. The SNP, rs7025486, is located in an intron of the DAB21P gene on chromosome 9q33. The gene encodes an inhibitor of cell growth and survival that is expressed in cardiovascular tissue.

"This is the sort of discovery that makes human genetics such an exciting field of endeavour. By incorporating this with other major genetic risk factors we include in our tests, such as those on 9p21, we are empowering physicians to identify greater numbers of those at high risk and who should therefore benefit from closer monitoring and prevention strategies. In the case of AAA, for example, this can be used along with traditional risk factors to identify those who should have ultrasound screening, leading to the detection of more aneurysms earlier, potentially saving lives," said Kari Stefansson, deCODE's executive chairman and president of research.

The first phase of the study analyzed several hundred thousand SNPs across the genomes of more than 30,000 Icelandic and Dutch participants, comparing the genotypes of those diagnosed with AAA to those of control subjects. A version of the rs7025486 SNP was found to confer a 20% increase in risk of AAA, an enlargment of the aorta that, if undiagnosed or left untreated, can lead to rupture, an event that is often fatal. The SNP was then analyzed in tens of thousands of patients and controls from a dozen countries to validate the finding in AAA and to check for association with other vascular diseases. In addition to replicating the association with risk of AAA, it was also found to confer risk of heart attack and early-onset heart attack, PAD and pulmonary embolism. The latter is noteworthy because it is a disease of the veins, and has traditionally been considered distinct from arterial disease. The paper, 'Genome-wide association study identifies sequence variants within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm,' is published online in Nature Genetics at http://www.nature.com/ng and will appear in an upcoming print edition of the journal.