Celera and Leiden University Medical Center Discover Genetic Markers Associated with Deep Vein...

Findings from Three Case-Control Studies Involving More Than 8,000 Individuals to Improve Identification of High Risk Individuals

ALAMEDA, Calif. & LEIDEN, The Netherlands -- 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 http://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.