Amini-Nekoo A, Futers T S, Moia M, Mannucci P M, Grant P J, Ariëns R A
Unit of Molecular Vascular Medicine, University of Leeds School of Medicine, Leeds, UK.
Br J Haematol. 2001 May;113(2):537-43. doi: 10.1046/j.1365-2141.2001.02752.x.
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 Val264Met 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.
组织因子途径抑制物（TFPI）可抑制组织因子诱导的凝血过程。TFPI的主要部分可被肝素释放出来。我们最近发现了8例血栓形成且肝素可释放的TFPI水平较低的患者，并对他们的TFPI基因进行了突变研究。结果发现，在肝素结合域存在一个由G到A的转换，该转换导致缬氨酸264突变为甲硫氨酸。在96名健康个体中，Val264Met多态性的等位基因频率为3%。在TFPI外显子IV中鉴定出一个沉默多态性（T→C），该多态性不会改变酪氨酸56。除了在8例患者中的1例检测到Val264Met外，在肝素可释放的TFPI水平较低的患者中未发现TFPI基因的其他突变。对317例深静脉血栓形成（DVT）患者和292名对照者的Val264Met分析显示，Val264Met与DVT之间无关联。然而，对122例DVT患者和126名对照者的总TFPI抗原水平进行的研究表明，TFPI水平与静脉血栓形成之间存在关联（P = 0.0001）。这些结果为静脉血栓形成与总TFPI水平之间的关系提供了证据，表明总TFPI水平可能是一个风险因素，而它们并不支持DVT与TFPI基因9个外显子中的突变之间存在联系。
