Genetic determinants of tissue factor pathway inhibitor plasma levels
Genetic determinants of tissue factor pathway inhibitor plasma levels
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DOI：
10.1160/th14-12-1043
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发表时间：
2015-08-01
影响因子：
6.7
通讯作者：
Gagnon, France
中科院分区：
文献类型：
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作者：
Dennis, Jessica;Kassam, Irfahan;Gagnon, France
组织因子途径抑制剂 (TFPI) 会阻碍血液凝固反应的早期阶段，低 TFPI 血浆水平会增加血栓形成的风险。 TFPI 血浆水平具有遗传性，但具体的遗传决定因素尚不清楚。我们对 TFPI 血浆水平的遗传风险因素进行了全面审查，并确定了 26 项研究。我们纳入了 16 项研究以及两项未发表的全基因组研究的结果，对 TFPI 及其启动子的四种常见遗传变异（rs5940、rs7586970/rs8176592、rs10931292 和 rs10153820）进行随机效应荟萃分析，并对 10 项研究进行了叙述性总结。 rs5940 与 TFPI 的所有测量值（游离、总和活性）相关，rs7586970 与总 TFPI 相关。 rs10931292 和 rs10153820 均未显示关联证据。叙述总结包括6个基因和遗传变异（TFPI中的P151L突变、PROS1、F5、APOE、GLA和JAK2中的V617F突变）以及全基因组连锁研究，并提出了未来的研究方向。系统评价的一个局限性是 TFPI 的测量方法不同。尽管如此，我们的综述发现强有力的证据表明，rs5940和rs7586970调节TFPI血浆水平，是血栓形成的候选危险因素，并且TFPI血浆水平的调节涉及TFPI基因以外的遗传因素。
Tissue factor pathway inhibitor (TFPI) impedes early stages of the blood coagulation response, and low TFPI plasma levels increase the risk of thrombosis. TFPI plasma levels are heritable, but specific genetic determinants are unclear. We conducted a comprehensive review of genetic risk factors for TFPI plasma levels and identified 26 studies. We included 16 studies, as well as results from two unpublished genome-wide studies, in random effects meta-analyses of four commonly reported genetic variants in TFPI and its promoter (rs5940, rs7586970/rs8176592, rs10931292, and rs10153820) and 10 studies were summarised narratively. rs5940 was associated with all measures of TFPI (free, total, and activity), and rs7586970 was associated with total TFPI. Neither rs10931292 nor rs10153820 showed evidence of association. The narrative summary included 6 genes and genetic variants (P151L mutation in TFPI, PROS1, F5, APOE, GLA, and V617F mutation in JAK2) as well as a genome-wide linkage study, and suggested future research directions. A limitation of the systematic review was the heterogeneous measurement of TFPI. Nonetheless, our review found robust evidence that rs5940 and rs7586970 moderate TFPI plasma levels and are candidate risk factors for thrombosis, and that the regulation of TFPI plasma levels involves genetic factors beyond the TFPI gene.