<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd"> <html> <head> <title>UTas ePrints - Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke</title> <script type="text/javascript" src="http://eprints.utas.edu.au/javascript/auto.js"><!-- padder --></script> <style type="text/css" media="screen">@import url(http://eprints.utas.edu.au/style/auto.css);</style> <style type="text/css" media="print">@import url(http://eprints.utas.edu.au/style/print.css);</style> <link rel="icon" href="/images/eprints/favicon.ico" type="image/x-icon" /> <link rel="shortcut icon" href="/images/eprints/favicon.ico" type="image/x-icon" /> <link rel="Top" href="http://eprints.utas.edu.au/" /> <link rel="Search" href="http://eprints.utas.edu.au/cgi/search" /> <meta content="Sayer, M.S." name="eprints.creators_name" /> <meta content="Cole, V.J." name="eprints.creators_name" /> <meta content="Adams, M.J." name="eprints.creators_name" /> <meta content="Baker, Ross I." name="eprints.creators_name" /> <meta content="Staton, J.M." name="eprints.creators_name" /> <meta content="" name="eprints.creators_id" /> <meta content="" name="eprints.creators_id" /> <meta content="Murray.Adams@utas.edu.au" name="eprints.creators_id" /> <meta content="" name="eprints.creators_id" /> <meta content="" name="eprints.creators_id" /> <meta content="article" name="eprints.type" /> <meta content="2007-10-31 02:09:02" name="eprints.datestamp" /> <meta content="2008-01-08 15:30:00" name="eprints.lastmod" /> <meta content="show" name="eprints.metadata_visibility" /> <meta content="Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke" name="eprints.title" /> <meta content="pub" name="eprints.ispublished" /> <meta content="321008" name="eprints.subjects" /> <meta content="restricted" name="eprints.full_text_status" /> <meta content="The present study aimed to determine whether four previously described polymorphisms found within the tissue factor pathway inhibitor (TFPI) gene are associated with free plasma TFPI levels or with TFPI activity as well as the risk of ischaemic stroke in stroke patients and control individuals. We conducted a case–control study of 162 first-ever ischaemic stroke cases and 170 randomly selected community control individuals. The TFPI genotype was determined for the T-287C, C-399T, Intron 7 C-33T, and Val264Met (G874A) polymorphisms. Free plasma TFPI and TFPI activity were measured during the first 7 days and 3–6 months after the acute stroke event. Free plasma TFPI levels were significantly lowered 3–6 months after stroke compared with levels observed in the patient group during the acute phase of the stroke (mean, 16.3 versus 22.46 ng/ml; PU0.046) and among the control group (mean, 16.3 versus 22.79 ng/ml; P<0.0001). Conversely, TFPI activity was significantly up-regulated during the acute phase (mean, 1.30 versus 1.11 U/ml; PU0.0051) and remained elevated 3–6 months later (mean, 1.28 versus 1.11 U/ml; PU0.03). The TFPI gene polymorphisms studied were not significantly associated with TFPI levels or activity, nor with the risk of ischaemic stroke. In conclusion, the TFPI activity and concentration in plasma varied significantly after an ischaemic stroke; however, these variations were not found to be due to the presence of any of the genetic mutations analysed in this study. Our results are consistent with the emerging model suggesting the lipoprotein-bound portion of TFPI has a significant influence on coagulation and diseases of haemostasis." name="eprints.abstract" /> <meta content="2007" 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="7" name="eprints.number" /> <meta content="703-708" name="eprints.pagerange" /> <meta content="TRUE" name="eprints.refereed" /> <meta content="0957-5235" name="eprints.issn" /> <meta content="http://www.bloodcoagulation.com" name="eprints.official_url" /> <meta content="References 1 McVey JH. Tissue factor pathway. Baillieres Best Pract Res Clin Haematol 1999; 12:361–372. 2 Dahm A, van HV, Bendz B, Rosendaal F, Bertina RM, Sandset PM. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood 2003; 101:4387–4392. 3 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988; 50:803– 813. 4 Lindahl AK, Abildgaard U, Stokke G. Release of extrinsic pathway inhibitor after heparin injection: increased response in cancer patients. Thromb Res 1990; 59:651–656. 5 Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze GJ Jr. Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood 1991; 78:387–393. 6 Lindahl AK, Jacobsen PB, Sandset PM, Abildgaard U. Tissue factor pathway inhibitor with high anticoagulant activity is increased in postheparin plasma and in plasma from cancer patients. Blood Coagul Fibrinolysis 1991; 2:713–721. 7 Nordfang O, Bjorn SE, Valentin S, Nielsen LS, Wildgoose P, Beck TC, Hedner U. The C-terminus of tissue factor pathway inhibitor is essential to its anticoagulant activity. Biochemistry 1991; 30:10371–10376. 8 Adams MJ, Thom J, Hankey GJ, Baker RI, Gilmore G, Staton J, Eikelboom JW. The tissue factor pathway in ischaemic stroke. Blood Coagul Fibrinolysis 2006; 17:527–532. 9 Girard TJ, Warren LA, Novotny WF, Likert KM, Brown SG, Miletich JP, Broze GJ Jr. Functional significance of the Kunitz-type inhibitory domains of lipoprotein-associated coagulation inhibitor. Nature 1989; 338:518–520. 10 Amini-Nekoo A, Futers TS, Moia M, Mannucci PM, Grant PJ, Ariens RA. Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis. Br J Haematol 2001; 113:537–543. 11 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 and prothrombin mutations. Thromb Haemost 2002; 88:195–199. 12 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 V264M substitution on plasma levels of TFPI. Arterioscler Thromb Vasc Biol 1999; 19:862–869. 13 Kleesiek K, Schmidt M, Gotting C, Brinkmann T, Prohaska W. A first mutation in the human tissue factor pathway inhibitor gene encoding [P151L]TFPI. Blood 1998; 92:3976–3977. 14 Mues GI, Sarode R. Allele frequencies of tissue factor pathway inhibitor polymorphisms in African-American, Hispanic and Caucasian populations. Thromb Haemost 2002; 88:875–877. 15 Wang L, Hirayasu K, Ishizawa M, Kobayashi Y. Purification of genomic DNA from human whole blood by isopropanol-fractionation with concentrated Nal and SDS. Nucleic Acids Res 1994; 22:1774–1775. 16 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 pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels. Thromb Haemost 2000; 84:244–249. 17 Miyata T, Sakata T, Kumeda K, Uchida K, Tsushima M, Fujimura H, et al. C-399T polymorphism in the promoter region of human tissue factor pathway inhibitor (TFPI) gene does not change the plasma TFPI antigen level and does not cause venous thrombosis. Thromb Haemost 1998; 80:345–346. 18 Moatti D, Meirhaeghe A, Ollivier V, Bauters C, Amouyel P, de Prost D. Polymorphisms of the tissue factor pathway inhibitor gene and the risk of restenosis after coronary angioplasty. Blood Coagul Fibrinolysis 2001; 12:317–323. 19 Arnaud E, Moatti D, Emmerich J, Aiach M, de Prost D. No link between the TFPI V264M mutation and venous thromboembolic disease. Thromb Haemost 1999; 82:159–160. 20 Novo G, Caplice N, Tantillo R, Bonura F, Simari R, Novo S. TFPI antigen and activity levels in patients with asymptomatic atherosclerosis and target organ acute and chronic complications. Int Angiol 2005; 24:366–371." name="eprints.referencetext" /> <meta content="Sayer, M.S. and Cole, V.J. and Adams, M.J. and Baker, Ross I. and Staton, J.M. (2007) Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke. Blood Coagulation and Fibrinolysis, 18 (7). pp. 703-708. ISSN 0957-5235" name="eprints.citation" /> <meta content="http://eprints.utas.edu.au/2341/1/Sayer_et_al_2007.pdf" name="eprints.document_url" /> <link rel="schema.DC" href="http://purl.org/DC/elements/1.0/" /> <meta content="Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke" name="DC.title" /> <meta content="Sayer, M.S." name="DC.creator" /> <meta content="Cole, V.J." name="DC.creator" /> <meta content="Adams, M.J." name="DC.creator" /> <meta content="Baker, Ross I." name="DC.creator" /> <meta content="Staton, J.M." name="DC.creator" /> <meta content="321008 Haematology" name="DC.subject" /> <meta content="The present study aimed to determine whether four previously described polymorphisms found within the tissue factor pathway inhibitor (TFPI) gene are associated with free plasma TFPI levels or with TFPI activity as well as the risk of ischaemic stroke in stroke patients and control individuals. We conducted a case–control study of 162 first-ever ischaemic stroke cases and 170 randomly selected community control individuals. The TFPI genotype was determined for the T-287C, C-399T, Intron 7 C-33T, and Val264Met (G874A) polymorphisms. Free plasma TFPI and TFPI activity were measured during the first 7 days and 3–6 months after the acute stroke event. Free plasma TFPI levels were significantly lowered 3–6 months after stroke compared with levels observed in the patient group during the acute phase of the stroke (mean, 16.3 versus 22.46 ng/ml; PU0.046) and among the control group (mean, 16.3 versus 22.79 ng/ml; P<0.0001). Conversely, TFPI activity was significantly up-regulated during the acute phase (mean, 1.30 versus 1.11 U/ml; PU0.0051) and remained elevated 3–6 months later (mean, 1.28 versus 1.11 U/ml; PU0.03). The TFPI gene polymorphisms studied were not significantly associated with TFPI levels or activity, nor with the risk of ischaemic stroke. In conclusion, the TFPI activity and concentration in plasma varied significantly after an ischaemic stroke; however, these variations were not found to be due to the presence of any of the genetic mutations analysed in this study. Our results are consistent with the emerging model suggesting the lipoprotein-bound portion of TFPI has a significant influence on coagulation and diseases of haemostasis." name="DC.description" /> <meta content="2007" name="DC.date" /> <meta content="Article" name="DC.type" /> <meta content="PeerReviewed" name="DC.type" /> <meta content="application/pdf" name="DC.format" /> <meta content="http://eprints.utas.edu.au/2341/1/Sayer_et_al_2007.pdf" name="DC.identifier" /> <meta content="http://www.bloodcoagulation.com" name="DC.relation" /> <meta content="Sayer, M.S. and Cole, V.J. and Adams, M.J. and Baker, Ross I. and Staton, J.M. (2007) Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke. Blood Coagulation and Fibrinolysis, 18 (7). pp. 703-708. 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border: solid 1px #ccc; padding: 3px"><tr> <td align="left"><a href="http://eprints.utas.edu.au/cgi/users/home">Login</a> | <a href="http://eprints.utas.edu.au/cgi/register">Create Account</a></td> <td align="right" style="white-space: nowrap"> <form method="get" accept-charset="utf-8" action="http://eprints.utas.edu.au/cgi/search" style="display:inline"> <input class="ep_tm_searchbarbox" size="20" type="text" name="q" /> <input class="ep_tm_searchbarbutton" value="Search" type="submit" name="_action_search" /> <input type="hidden" name="_order" value="bytitle" /> <input type="hidden" name="basic_srchtype" value="ALL" /> <input type="hidden" name="_satisfyall" value="ALL" /> </form> </td> </tr></table></td></tr> <tr> <td class="toplinks"><!-- InstanceBeginEditable name="content" --> <div align="center"> <table width="720" class="ep_tm_main"><tr><td align="left"> <h1 class="ep_tm_pagetitle">Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke</h1> <p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Sayer, M.S.</span> and <span class="person_name">Cole, V.J.</span> and <span class="person_name">Adams, M.J.</span> and <span class="person_name">Baker, Ross I.</span> and <span class="person_name">Staton, J.M.</span> (2007) <xhtml:em>Polymorphisms in the tissue factor pathway inhibitor gene are not associated with ischaemic stroke.</xhtml:em> Blood Coagulation and Fibrinolysis, 18 (7). pp. 703-708. 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/2341/1/Sayer_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/2341/1/Sayer_et_al_2007.pdf"><span class="ep_document_citation">PDF</span></a> - Full text restricted - Requires a PDF viewer<br />106Kb</td><td><form method="get" accept-charset="utf-8" action="http://eprints.utas.edu.au/cgi/request_doc"><input accept-charset="utf-8" value="2998" name="docid" type="hidden" /><div class=""><input value="Request a copy" name="_action_null" class="ep_form_action_button" onclick="return EPJS_button_pushed( '_action_null' )" type="submit" /> </div></form></td></tr></table><p style="margin-bottom: 1em" class="not_ep_block">Official URL: <a href="http://www.bloodcoagulation.com">http://www.bloodcoagulation.com</a></p><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">The present study aimed to determine whether four previously described polymorphisms found within the tissue factor pathway inhibitor (TFPI) gene are associated with free plasma TFPI levels or with TFPI activity as well as the risk of ischaemic stroke in stroke patients and control individuals. We conducted a case–control study of 162 first-ever ischaemic stroke cases and 170 randomly selected community control individuals. The TFPI genotype was determined for the T-287C, C-399T, Intron 7 C-33T, and Val264Met (G874A) polymorphisms. Free plasma TFPI and TFPI activity were measured during the first 7 days and 3–6 months after the acute stroke event. Free plasma TFPI levels were significantly lowered 3–6 months after stroke compared with levels observed in the patient group during the acute phase of the stroke (mean, 16.3 versus 22.46 ng/ml; PU0.046) and among the control group (mean, 16.3 versus 22.79 ng/ml; P<0.0001). Conversely, TFPI activity was significantly up-regulated during the acute phase (mean, 1.30 versus 1.11 U/ml; PU0.0051) and remained elevated 3–6 months later (mean, 1.28 versus 1.11 U/ml; PU0.03). The TFPI gene polymorphisms studied were not significantly associated with TFPI levels or activity, nor with the risk of ischaemic stroke. In conclusion, the TFPI activity and concentration in plasma varied significantly after an ischaemic stroke; however, these variations were not found to be due to the presence of any of the genetic mutations analysed in this study. Our results are consistent with the emerging model suggesting the lipoprotein-bound portion of TFPI has a significant influence on coagulation and diseases of haemostasis.</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">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">2341</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">31 Oct 2007 13:09</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=2341;">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=2341">item control page</a></p> </td></tr></table> </div> <!-- InstanceEndEditable --></td> </tr> <tr> <td><!-- #BeginLibraryItem "/Library/footer_eprints.lbi" --> <table width="795" border="0" align="left" cellpadding="0" class="footer"> <tr valign="top"> <td colspan="2"><div align="center"><a href="http://www.utas.edu.au">UTAS home</a> | <a href="http://www.utas.edu.au/library/">Library home</a> | <a href="/">ePrints home</a> | <a href="/contact.html">contact</a> | <a href="/information.html">about</a> | <a href="/view/">browse</a> | <a href="/perl/search/simple">search</a> | <a href="/perl/register">register</a> | <a href="/perl/users/home">user area</a> | <a href="/help/">help</a></div><br /></td> </tr> <tr><td colspan="2"><p><img src="/images/eprints/footerline.gif" width="100%" height="4" /></p></td></tr> <tr valign="top"> <td width="68%" class="footer">Authorised by the University Librarian<br /> © University of Tasmania ABN 30 764 374 782<br /> <a href="http://www.utas.edu.au/cricos/">CRICOS Provider Code 00586B</a> | <a href="http://www.utas.edu.au/copyright/copyright_disclaimers.html">Copyright & Disclaimers</a> | <a href="http://www.utas.edu.au/accessibility/index.html">Accessibility</a> | <a href="http://eprints.utas.edu.au/feedback/">Site Feedback</a> </td> <td width="32%"><div align="right"> <p align="right" class="NoPrint"><a href="http://www.utas.edu.au/"><img src="http://www.utas.edu.au/shared/logos/unioftasstrip.gif" alt="University of Tasmania Home Page" width="260" height="16" border="0" align="right" /></a></p> <p align="right" class="NoPrint"><a href="http://www.utas.edu.au/"><br /> </a></p> </div></td> </tr> <tr valign="top"> <td><p> </p></td> <td><div align="right"><span class="NoPrint"><a href="http://www.eprints.org/software/"><img src="/images/eprintslogo.gif" alt="ePrints logo" width="77" height="29" border="0" align="bottom" /></a></span></div></td> </tr> </table> <!-- #EndLibraryItem --> <div align="center"></div></td> </tr> </table> </body> </html>