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<title>UTas ePrints - Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden</title>
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<meta content="Lincz, L.F." name="eprints.creators_name" />
<meta content="Adams, M.J." name="eprints.creators_name" />
<meta content="Scorgie, F.E." name="eprints.creators_name" />
<meta content="Thom, J." name="eprints.creators_name" />
<meta content="Baker, Ross I." name="eprints.creators_name" />
<meta content="Seldon, M." name="eprints.creators_name" />
<meta content="article" name="eprints.type" />
<meta content="2007-09-27" name="eprints.datestamp" />
<meta content="2008-01-08 15:30:00" name="eprints.lastmod" />
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<meta content="Polymorphisms of the tissue factor pathway inhibitor gene
are associated with venous thromboembolism in the
antiphospholipid syndrome and carriers of factor V Leiden" name="eprints.title" />
<meta content="pub" name="eprints.ispublished" />
<meta content="321008" name="eprints.subjects" />
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<meta content="antiphospholipid syndrome, factor V Leiden, tissue factor
pathway inhibitor, venous thrombosis" name="eprints.keywords" />
<meta content="The definitive version is available online at www.bloodcoagulation.com/" name="eprints.note" />
<meta content="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." name="eprints.abstract" />
<meta content="2007-09" name="eprints.date" />
<meta content="published" name="eprints.date_type" />
<meta content="Blood Coagulation and Fibrinolysis" name="eprints.publication" />
<meta content="18" name="eprints.volume" />
<meta content="6" name="eprints.number" />
<meta content="559-564" name="eprints.pagerange" />
<meta content="10.1097/MBC.0b013e3281eec977" name="eprints.id_number" />
<meta content="UNSPECIFIED" name="eprints.thesis_type" />
<meta content="TRUE" name="eprints.refereed" />
<meta content="0957-5235" name="eprints.issn" />
<meta content="http://dx.doi.org/10.1097/MBC.0b013e3281eec977" name="eprints.official_url" />
<meta content="1 Wun TC, Kretzmer KK, Girard TJ, Miletich JP, Broze GJ Jr. Cloning and
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Analysis of the tissue factor pathway inhibitor gene and antigen levels in
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7 Lwaleed BA, Bass PS. Tissue factor pathway inhibitor: structure, biology
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International consensus statement on an update of the classification criteria
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18 Moatti D, Haidar B, Fumeron F, Gauci L, Boudvillain O, Seknadji P, et al.
A new T-287C polymorphism in the 50 regulatory region of the tissue factor
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19 Moatti D, Seknadji P, Galand C, Poirier O, Fumeron F, Desprez S, et al.
Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients
with acute coronary syndromes and in healthy subjects: impact of the
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20 Sandset PM, Larsen ML, Abildgaard U, Lindahl AK, Odegaard OR.
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21 Ameziane N, Seguin C, Borgel D, Fumeron F, Moatti D, Alhenc-Gelas M,
et al. The -33T->C polymorphism in intron 7 of the TFPI gene influences
the risk of venous thromboembolism, independently of the factor V Leiden
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22 Miyata T, Sakata T, Kumeda K, Uchida K, Tsushima M, Fujimura H, et al.
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89:985-990.
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31 Hubbard AR, Weller LJ, Gray E. Measurement of tissue factor pathway
inhibitor in normal and postheparin plasma. Blood Coagul Fibrinolysis
1994; 5:819-823.
32 Jeske W, Hoppensteadt D, Fareed J, Bermes E. Measurement of functional
and immunologic levels of tissue factor pathway inhibitor. Some
methodologic considerations. Blood Coagul Fibrinolysis 1995; 6 (Suppl 1):
S73-S80.
33 Adams MJ, Oostryck R. A comparative study of functional assays for tissue
factor pathway inhibitor using normal plasma and clinical samples. Blood
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34 Bognacki J, Hammelburger J. Functional and immunologic methods for the
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35 Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP. Structure and biology of tissue
factor pathway inhibitor. Thromb Haemost 2001; 86:959-972." name="eprints.referencetext" />
<meta content="Lincz, L.F. and Adams, M.J. and Scorgie, F.E. and Thom, J. and Baker, Ross I. 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, 18 (6). pp. 559-564. ISSN 0957-5235" name="eprints.citation" />
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<meta content="Polymorphisms of the tissue factor pathway inhibitor gene
are associated with venous thromboembolism in the
antiphospholipid syndrome and carriers of factor V Leiden" name="DC.title" />
<meta content="Lincz, L.F." name="DC.creator" />
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<meta content="321008 Haematology" name="DC.subject" />
<meta content="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." name="DC.description" />
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<h1 class="ep_tm_pagetitle">Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden</h1>
<p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Lincz, L.F.</span> and <span class="person_name">Adams, M.J.</span> and <span class="person_name">Scorgie, F.E.</span> and <span class="person_name">Thom, J.</span> and <span class="person_name">Baker, Ross I.</span> and <span class="person_name">Seldon, M.</span> (2007) <xhtml:em>Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden.</xhtml:em> Blood Coagulation and Fibrinolysis, 18 (6). pp. 559-564. ISSN 0957-5235</p><p style="margin-bottom: 1em" class="not_ep_block"></p><table style="margin-bottom: 1em" class="not_ep_block"><tr><td valign="top" style="text-align:center"><a href="http://eprints.utas.edu.au/1768/1/Lincz_et_al_2007.pdf"><img alt="[img]" src="http://eprints.utas.edu.au/style/images/fileicons/application_pdf.png" class="ep_doc_icon" border="0" /></a></td><td valign="top"><a href="http://eprints.utas.edu.au/1768/1/Lincz_et_al_2007.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />111Kb</td></tr></table><p style="margin-bottom: 1em" class="not_ep_block">Official URL: <a href="http://dx.doi.org/10.1097/MBC.0b013e3281eec977">http://dx.doi.org/10.1097/MBC.0b013e3281eec977</a></p><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">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.</p></div><table style="margin-bottom: 1em" cellpadding="3" class="not_ep_block" border="0"><tr><th valign="top" class="ep_row">Item Type:</th><td valign="top" class="ep_row">Article</td></tr><tr><th valign="top" class="ep_row">Additional Information:</th><td valign="top" class="ep_row">The definitive version is available online at www.bloodcoagulation.com/</td></tr><tr><th valign="top" class="ep_row">Keywords:</th><td valign="top" class="ep_row">antiphospholipid syndrome, factor V Leiden, tissue factor
pathway inhibitor, venous thrombosis</td></tr><tr><th valign="top" class="ep_row">Subjects:</th><td valign="top" class="ep_row"><a href="http://eprints.utas.edu.au/view/subjects/321008.html">320000 Medical and Health Sciences > 321000 Clinical Sciences > 321008 Haematology</a></td></tr><tr><th valign="top" class="ep_row">ID Code:</th><td valign="top" class="ep_row">1768</td></tr><tr><th valign="top" class="ep_row">Deposited By:</th><td valign="top" class="ep_row"><span class="ep_name_citation"><span class="person_name">Dr Murray J Adams</span></span></td></tr><tr><th valign="top" class="ep_row">Deposited On:</th><td valign="top" class="ep_row">27 Sep 2007</td></tr><tr><th valign="top" class="ep_row">Last Modified:</th><td valign="top" class="ep_row">09 Jan 2008 02:30</td></tr><tr><th valign="top" class="ep_row">ePrint Statistics:</th><td valign="top" class="ep_row"><a target="ePrintStats" href="/es/index.php?action=show_detail_eprint;id=1768;">View statistics for this ePrint</a></td></tr></table><p align="right">Repository Staff Only: <a href="http://eprints.utas.edu.au/cgi/users/home?screen=EPrint::View&eprintid=1768">item control page</a></p>
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