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

Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagu lation. 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 c oding for Valine264Methionine in the heparin-binding domain was found. The Val264Met polymorphism had an allele frequency of 3% in 96 healthy individu als, A silent polymorphism was identified in TFPI exon IV (T-->C), which do es not alter Tyrosine 56. Apart from Val264Met, which was detected in one o ut of the eight patients, no other mutations in the TFPI gene were found Va l264Met in 317 patients with deep vein thrombosis (DVT) and 292 controls sh owed no association between Val264Met and DVT, However, a study of total TF PI antigen levels in 122 DVT patients and 126 controls demonstrated an asso ciation between TFPI levels and venous thrombosis (P = 0.0001). These resul ts provide evidence for a relationship between venous thrombosis and total TFPI level as a possible risk factor, whereas they do not support a link be tween DVT and mutations in the nine exons of the TFPI gene.