Genetic variants influencing white blood cell counts are linked to increased risk of heart attack and asthma; variants are being integrated into deCODEme™
Reykjavik, ICELAND, February 9, 2009 – In a paper published today, scientists at deCODE genetics (Nasdaq:DCGN) and academic colleagues from four continents present a novel insight into the connection between inflammation and heart disease. Through a genome-wide search in some 10,000 Icelanders, the deCODE team discovered several common single-letter variations in the sequence of the human genome (SNPs) that increase levels of eosinophils in the bloodstream. These are a type of white blood cell that fights parasite infection and mediates inflammation. One of these SNPs, located on chromsome 12q24, was then shown to confer increased risk of heart attack through analysis of the genomes of more than 46,000 patients and controls from Iceland, New Zealand, Italy, and the United States. Given the established role of eosinophils in asthma, the deCODE team also analyzed the eosinophil SNPs in more than 50,000 asthmatics and healthy control subjects from the countries above as well as from Germany, Sweden, Australia, and South Korea. A SNP on chromosome 2q12 was associated with increased risk of asthma, and three other SNPs were associated with risk of atopic asthma.
“This is a great example of how our population data and approach enable us to examine complex questions from multiple vantage points. There is broad interest in the connection between inflammation and cardiovascular disease, and our own discoveries on chromosome 9p21 and in the leukotriene pathway have helped to drive this interest. And in today’s work, we started by identifying genetic variants involved in a known inflammatory process and then went on to demonstrate that some of those variants were also risk factors for both heart attack and asthma. These discoveries may be used both in drug discovery and to build out our tools for DNA-based risk assessment of these diseases. We are already integrating these findings into our deCODEme™ scans,” said Kari Stefansson, CEO of deCODE and senior author on the study.
The SNP on chromosome 12q24 associated with heart attack risk is in the SH2B3 gene (also known as LNK), which encodes the SH2B3 protein. This protein is known to be involved in inflammation, as well as in hematopoiesis, that is the formation and development of blood cells. The paper, “Sequence variants associated with eosoniphil numbers associate with asthma and myocardial infarction,” is published today in the online edition of Nature Genetics, at www.nature.com/ng.
deCODE would like to thank the many thousands of participants and the large group of collaborating scientists and clinicians who took part in this study. The genotyping in the myocardial infarction study was supported in part by a grant from the US National Institutes of Health Heart, Lung and Blood Institute (SR01HL089650-01).
deCODE is a bio-pharmaceutical company developing drugs and DNA-based tests to improve the treatment, diagnosis and prevention of common diseases. Its lead therapeutic programs, which leverage the company’s expertise in chemistry and structural biology, include DG041, an antiplatelet compound being developed for the prevention of arterial thrombosis; DG051 and DG031, compounds targeting the leukotriene pathway for the prevention of heart attack; and DG071 and a platform for other PDE4 modulators with therapeutic applications in Alzheimer’s disease and other conditions. deCODE is a global leader in human genetics, and has identified key variations in the genome (SNPs) conferring increased risk of major public health challenges from cardiovascular disease to cancer. Based upon these discoveries deCODE has brought to market a growing range of DNA-based tests for gauging risk and empowering prevention of common diseases. Through its CLIA-registered laboratory, deCODE is offers deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProstateCancer™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer™, for the common forms of breast cancer. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com; on our diagnostics site at www.decodediagnostics.com; for our pioneering personal genome analysis service and new Cardio and Cancer scans, integrating the genetic variants included in these tests and those linked to another twenty common diseases, at www.decodeme.com; and on our blog at www.decodeyou.com.
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