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Current | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 2000 Celera and Leiden University Medical Center Discover Genetic Markers Associated with Deep Vein Thrombosis Alameda, CA, and Leiden, The Netherlands - March 18, 2008 Celera (NYSE:CRA), an Applera Corporation business, and researchers at the Leiden University Medical Center in the Netherlands, today announced the publication of a paper describing the identification of several novel gene variants that each are associated with approximately 50 percent increased risk of deep vein thrombosis (DVT). The paper is scheduled to appear in the March 19, 2008 edition of the Journal of the American Medical Association, and is currently available on the journal’s website at jama.ama-assn.org/. Researchers from the two organizations investigated whether any of 19,682 gene variants (primarily missense single nucleotide polymorphisms, or SNPs) were associated with DVT in three case-control research studies including over 8,000 individuals. A key finding of the paper was the identification of seven gene variants that were associated with DVT. Of these seven gene variants, the strongest evidence for association with DVT was found for three common variants of CYP4V2, a novel cytochrome p450 gene, SERPINC1, and GP6. These gene variants are either in, or near, genes that have a clear role in blood coagulation. Since it has been suggested that thrombosis is a multicausal disease due to multiple risk factors, the current findings complement the two common genetic variants, Factor V Leiden and prothrombin G20210A, that have been consistently found to be associated with DVT. In the current study, the CYP4V2 gene variant, which is present in over 50 percent of the population, was found to increase risk of DVT 1.5 fold. In contrast, Factor V Leiden and Factor II (prothrombin) are present in only 1 to 8 percent of the population, although carriers of these variants have been found to have higher levels of risk for DVT. The proportion of all thrombotic events attributable to the risk factor in the population for CYP4V2 carriers was therefore approximately the same as for Factor V Leiden and Factor II, suggesting clinical utility in identifying high-risk individuals. The SERPINC1 gene encodes antithrombin, a serine protease inhibitor located on chromosome 1 that plays a central role in natural anticoagulation. The GP6 gene encodes glycoprotein VI, a 58-kDa platelet membrane glycoprotein that plays a crucial role in the collagen-induced activation and aggregation of platelets and may play a role in DVT. “It’s been ten years since our center discovered Factor V Leiden and the prothrombin 20210A mutation, and now we have identified several new common risk factors for thrombosis,” said Professor Frits Rosendaal, M.D., Ph.D. at the Leiden University Medical Center, the lead author of the study. “It is striking that most of these genetic variants are connected to the clotting system, indicating that this is well-characterized. Although these new risk factors are not as strong as the ones known so far, their importance lies in the high prevalence.” “The determinants of the severity of deep vein thrombosis are complex, but rigorous studies such as this one provide sound evidence of a major genetic component,” said Tom White, Ph.D., Chief Scientific Officer at Celera. “Building on these studies and in line with our vision for personalized disease management, physicians and patients should eventually have access to blood tests that provide a measure of each individual’s respective genetic risk of developing this disease, which in turn will enable earlier therapeutic intervention.” About Deep Vein Thrombosis About the studies at the Leiden University Medical Center The SNPs described in this paper were associated with DVT in a total of 3,155 cases and 5,087 controls in 3 studies drawn from two large population-based studies: the Leiden Thrombophilia Study (LETS) and the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA study). In the LETS study, 474 patients who were 70 years or younger and without a known malignancy were recruited, from three anticoagulation clinics in The Netherlands. For each patient, an age- and sex-matched control participant without a history of DVT was enrolled. The MEGA study enrolled patients aged 18 to 70 years who presented with their first diagnosis of DVT or PE. Control subjects included partners of patients and random population control subjects frequency-matched on age and sex to the patient group. For the present analyses, the MEGA study was split to form 2 case-control samples: the first subset, MEGA-1, included 1,398 cases and 1,757 controls, and the remaining second subset MEGA-2 comprised of 1,314 cases and 2,877 controls. This design was chosen to enable the replication of positive findings and avoid false positive findings, which is a major issue in studies in which very large numbers of variants are tested. The design with three large sample sets, including a quantification of this effect by the ‘false discovery rate,’ makes it highly likely that the findings are correct. About Applera Corporation and Celera Forward-Looking Statements Copyright© 2008. Applera Corporation. All rights reserved. Applera, Applied Biosystems and Celera are registered trademarks of Applera Corporation or its subsidiaries in the US and certain other countries. Contacts:
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