组织因子和组织因子途径抑制物基因多态性对稳定型冠状动脉疾病中凝血酶生成的影响。

The influence of tissue factor and tissue factor pathway inhibitor polymorphisms on thrombin generation in stable coronary artery disease.

作者信息

Opstad Trine B, Pettersen Alf-Aage R, Bratseth Vibeke, Arnesen Harald, Seljeflot Ingebjørg

机构信息

Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Oslo, Norway.

出版信息

Pathophysiol Haemost Thromb. 2010;37(2-4):98-103. doi: 10.1159/000327491. Epub 2011 May 10.

DOI:10.1159/000327491

PMID:21555871

Abstract

In patients with stable coronary heart disease (n = 1,001) we investigated the influence of tissue factor (TF) and TF pathway inhibitor (TFPI) polymorphisms on thrombin generation in vivo, measured by prothrombin fragment (F) 1 and 2, and the potential to generate thrombin ex vivo, measured by the calibrated automated thrombogram assay. Additionally, circulating levels of TF and TFPI were correlated to the different parameters of thrombin generation. The TF 5466 and TFPI -399 polymorphisms associated with higher thrombin generation in vivo, the latter also with a prolonged lag time of the thrombin generation ex vivo(p < 0.05 for all).The TF -1812 TT and the TF -603 GG genotypes were associated with lower peak thrombin and a decreased average net rate of thrombin activation during the propagation phases (p ≤ 0.05), and the TFPI -33 TC genotype with prolonged lag time (p < 0.05) and additionally time to peak (p = 0.06). Strong correlations between TFPI levels, prothrombin fragment 1 and 2 as well as calibrated automated thrombogram parameters were observed.

摘要

在患有稳定型冠心病的患者（n = 1001）中，我们研究了组织因子（TF）和TF途径抑制剂（TFPI）基因多态性对体内凝血酶生成的影响（通过凝血酶原片段（F）1和2进行测量），以及体外生成凝血酶的潜力（通过校准自动血栓图测定法进行测量）。此外，TF和TFPI的循环水平与凝血酶生成的不同参数相关。TF 5466和TFPI -399基因多态性与体内较高的凝血酶生成相关，后者还与体外凝血酶生成的延迟时间延长相关（所有p < 0.05）。TF -1812 TT和TF -603 GG基因型与传播阶段较低的凝血酶峰值和降低的凝血酶激活平均净速率相关（p≤0.05），而TFPI -33 TC基因型与延迟时间延长（p < 0.05）以及到达峰值的时间延长相关（p = 0.06）。观察到TFPI水平、凝血酶原片段1和2以及校准自动血栓图参数之间存在强相关性。