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Mar 18, 2008

Scientists Identify SNPs Linked to Deep Vein Thrombosis

  • Celera and researchers at the Leiden University Medical Center identified novel gene variants that are each associated with an approximately 50% increased risk of deep vein thrombosis (DVT). 

    Researchers from the two organizations used three case-control research studies, which included over 8,000 individuals. They report identifying seven gene variants associated with DVT. Of these, the strongest association evidence was found for common variants of CYP4V2, which is a cytochrome p450 gene, SERPINC1, and GP6. These gene variants are either in or near genes that have a clear role in blood coagulation.

    The CYP4V2 gene variant, which is present in over 50% of the population, was found to increase risk of DVT 1.5-fold. In contrast, Factor V Leiden and Factor II, previously associated with DVT, are present in only 1–8% 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, according to the researchers.

    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 role in the collagen-induced activation and aggregation of platelets and may play a role in DVT.

    “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,” says Frits Rosendaal, M.D., Ph.D., at the Leiden University Medical Center and the lead author of the study.

    The paper is scheduled to appear in the March 19, edition of the Journal of the American Medical Association.



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