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Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden

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Lincz, LF, Adams, MJ, Scorgie, FE, Thom, J, Baker, RI and Seldon, M 2007 , 'Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden' , Blood Coagulation and Fibrinolysis, vol. 18, No. 6 , pp. 559-564 , doi: 10.1097/MBC.0b013e3281eec977.

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Abstract

Polymorphisms within the tissue factor pathway inhibitor (TFPI) gene may determine TFPI expression and increase the risk of venous thromboembolism (VTE) in predisposed individuals. We tested this hypothesis by comparing TFPI activity and the frequency of common TFPI polymorphisms, -33T->C, -399C->T and -287T->C, in patients with antiphospholipid syndrome (APS) (n = 24) or factor V Leiden (n = 44) who had a history of VTE (n = 26), compared with those without VTE (n = 42) and also with normal control individuals (n = 56). TFPI activity was measured using a modified amidolytic assay and genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. We found that only APS patients with a history of venous thrombosis had TFPI activity levels significantly different from control individuals (1.77 +/- 0.60 vs 0.77 +/- 0.19 U/ml; P = 0.0001), and this was associated with inheritance of the TFPI -33C allele (1.70 +/- 0.72 U/ml for TC/CC genotypes vs 0.97 +/- 0.56 U/ml for TT; P = 0.01). Multivariate analysis of APS and factor V Leiden patients revealed that the greatest independent contributor to VTE was TFPI activity (adjusted odds ratio = 16.84; 95% confidence interval = 2.47-114.36, P = 0.004), while inheritance of either the TFPI -33C or -399T alleles each increased the odds of VTE by nearly 13 times (95% confidence interval = 2.39-69.91, P = 0.003; and 95% confidence interval = 2.25-71.23, P = 0.004, respectively). These results indicate that the TFPI -33T->C and -399C->T polymorphisms are significantly associated with venous thrombosis in the presence of other risk factors, especially APS, and may be clinically relevant in patients who are prone to hypercoagulability.

Item Type: Article
Authors/Creators:Lincz, LF and Adams, MJ and Scorgie, FE and Thom, J and Baker, RI and Seldon, M
Keywords: antiphospholipid syndrome, factor V Leiden, tissue factor pathway inhibitor, venous thrombosis
Journal or Publication Title: Blood Coagulation and Fibrinolysis
ISSN: 0957-5235
DOI / ID Number: 10.1097/MBC.0b013e3281eec977
Additional Information:

The definitive version is available online at www.bloodcoagulation.com/

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