Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis

Ali Amini Nekoo, T. Simon Futers, Marco Moia, Pier M. Mannucci, Peter J. Grant, R. A S Ariëns

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation. The major part of TFPI is releasable by heparin. We recently found eight patients with thrombosis and low levels of heparin-releasable TFPI in whom we investigated the TFPI gene for mutations. A transition of G to A coding for Valine264Methionine in the heparin-binding domain was found. The Val264Met polymorphism had an allele frequency of 3% in 96 healthy individuals. A silent polymorphism was identified in TFPI exon IV (T→C), which does not alter Tyrosine 56. Apart from Val264Met, which was detected in one out of the eight patients, no other mutations in the TFPI gene were found in patients with low heparin-releasable TFPI. Analysis of Val264Met in 317 patients with deep vein thrombosis (DVT) and 292 controls showed no association between Val264-Met and DVT. However, a study of total TFPI antigen levels in 122 DVT patients and 126 controls demonstrated an association between TFPI levels and venous thrombosis (P = 0.0001). These results provide evidence for a relationship between venous thrombosis and total TFPI level as a possible risk factor, whereas they do not support a link between DVT and mutations in the nine exons of the TFPI gene.

Original languageEnglish
Pages (from-to)537-543
Number of pages7
JournalBritish Journal of Haematology
Volume113
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Venous Thrombosis
Antigens
Genes
Heparin
Mutation
Exons
lipoprotein-associated coagulation inhibitor
Thromboplastin
Gene Frequency
Tyrosine
Thrombosis

Keywords

  • Antigen levels
  • Heparin
  • Polymorphisms
  • TFPI gene exons
  • Thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis. / Nekoo, Ali Amini; Simon Futers, T.; Moia, Marco; Mannucci, Pier M.; Grant, Peter J.; Ariëns, R. A S.

In: British Journal of Haematology, Vol. 113, No. 2, 2001, p. 537-543.

Research output: Contribution to journalArticle

Nekoo, Ali Amini ; Simon Futers, T. ; Moia, Marco ; Mannucci, Pier M. ; Grant, Peter J. ; Ariëns, R. A S. / Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis. In: British Journal of Haematology. 2001 ; Vol. 113, No. 2. pp. 537-543.
@article{c241a37a0152424493b1eecd91a13a94,
title = "Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis",
abstract = "Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation. The major part of TFPI is releasable by heparin. We recently found eight patients with thrombosis and low levels of heparin-releasable TFPI in whom we investigated the TFPI gene for mutations. A transition of G to A coding for Valine264Methionine in the heparin-binding domain was found. The Val264Met polymorphism had an allele frequency of 3{\%} in 96 healthy individuals. A silent polymorphism was identified in TFPI exon IV (T→C), which does not alter Tyrosine 56. Apart from Val264Met, which was detected in one out of the eight patients, no other mutations in the TFPI gene were found in patients with low heparin-releasable TFPI. Analysis of Val264Met in 317 patients with deep vein thrombosis (DVT) and 292 controls showed no association between Val264-Met and DVT. However, a study of total TFPI antigen levels in 122 DVT patients and 126 controls demonstrated an association between TFPI levels and venous thrombosis (P = 0.0001). These results provide evidence for a relationship between venous thrombosis and total TFPI level as a possible risk factor, whereas they do not support a link between DVT and mutations in the nine exons of the TFPI gene.",
keywords = "Antigen levels, Heparin, Polymorphisms, TFPI gene exons, Thrombosis",
author = "Nekoo, {Ali Amini} and {Simon Futers}, T. and Marco Moia and Mannucci, {Pier M.} and Grant, {Peter J.} and Ari{\"e}ns, {R. A S}",
year = "2001",
doi = "10.1046/j.1365-2141.2001.02752.x",
language = "English",
volume = "113",
pages = "537--543",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "2",

}

TY - JOUR

T1 - Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis

AU - Nekoo, Ali Amini

AU - Simon Futers, T.

AU - Moia, Marco

AU - Mannucci, Pier M.

AU - Grant, Peter J.

AU - Ariëns, R. A S

PY - 2001

Y1 - 2001

N2 - Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation. The major part of TFPI is releasable by heparin. We recently found eight patients with thrombosis and low levels of heparin-releasable TFPI in whom we investigated the TFPI gene for mutations. A transition of G to A coding for Valine264Methionine in the heparin-binding domain was found. The Val264Met polymorphism had an allele frequency of 3% in 96 healthy individuals. A silent polymorphism was identified in TFPI exon IV (T→C), which does not alter Tyrosine 56. Apart from Val264Met, which was detected in one out of the eight patients, no other mutations in the TFPI gene were found in patients with low heparin-releasable TFPI. Analysis of Val264Met in 317 patients with deep vein thrombosis (DVT) and 292 controls showed no association between Val264-Met and DVT. However, a study of total TFPI antigen levels in 122 DVT patients and 126 controls demonstrated an association between TFPI levels and venous thrombosis (P = 0.0001). These results provide evidence for a relationship between venous thrombosis and total TFPI level as a possible risk factor, whereas they do not support a link between DVT and mutations in the nine exons of the TFPI gene.

AB - Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation. The major part of TFPI is releasable by heparin. We recently found eight patients with thrombosis and low levels of heparin-releasable TFPI in whom we investigated the TFPI gene for mutations. A transition of G to A coding for Valine264Methionine in the heparin-binding domain was found. The Val264Met polymorphism had an allele frequency of 3% in 96 healthy individuals. A silent polymorphism was identified in TFPI exon IV (T→C), which does not alter Tyrosine 56. Apart from Val264Met, which was detected in one out of the eight patients, no other mutations in the TFPI gene were found in patients with low heparin-releasable TFPI. Analysis of Val264Met in 317 patients with deep vein thrombosis (DVT) and 292 controls showed no association between Val264-Met and DVT. However, a study of total TFPI antigen levels in 122 DVT patients and 126 controls demonstrated an association between TFPI levels and venous thrombosis (P = 0.0001). These results provide evidence for a relationship between venous thrombosis and total TFPI level as a possible risk factor, whereas they do not support a link between DVT and mutations in the nine exons of the TFPI gene.

KW - Antigen levels

KW - Heparin

KW - Polymorphisms

KW - TFPI gene exons

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=0035014293&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035014293&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.2001.02752.x

DO - 10.1046/j.1365-2141.2001.02752.x

M3 - Article

C2 - 11380428

AN - SCOPUS:0035014293

VL - 113

SP - 537

EP - 543

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -