Significant genetic association of a functional TFPI variant with circulating fibrinogen levels and coronary artery disease.
Significant genetic association of a functional TFPI variant with circulating fibrinogen levels and coronary artery disease.
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功能性 TFPI 变异与循环纤维蛋白原水平和冠状动脉疾病存在显着的遗传关联。
DOI：
10.1007/s00438-017-1365-6
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Wang QK
中科院分区：
文献类型：
--
作者：
Naji DH;Tan C;Han F;Zhao Y;Wang J;Wang D;Fa J;Li S;Chen S;Chen Q;Xu C;Wang QK
组织因子途径抑制物（TFPI）基因编码蛋白酶抑制剂，其在调节血液凝固中具有关键作用。TFPI中的一些基因组变体先前与血浆TFPI水平相关，然而，TFPI变体是否与其他凝血因子相关仍有待进一步确定。在这项研究中，我们对2，313名研究受试者进行了一项基于人群的大型研究，以获取凝血数据，包括纤维蛋白原水平、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）和凝血酶时间（TT）。我们发现TFPI变体rs10931292（一种反式激活功能降低的功能性启动子变体）与血浆纤维蛋白原水平升高显著相关（隐性模型下P=0.017），但与PT、APTT或TT无关（P>0.05）。通过对4，479例CAD患者和3，628例对照的大型病例对照关联研究，我们在隐性模型下确定了rs10931292与CAD之间的显著关联（OR = 1.23，P = 0.005）。我们首次发现TFPI变异与纤维蛋白原水平和CAD风险显著相关。我们的发现有助于阐明纤维蛋白原水平和CAD发展的遗传基础和生物学途径。
The tissue factor pathway inhibitor (TFPI) gene encodes a protease inhibitor with a critical role in regulation of blood coagulation. Some genomic variants in TFPI were previously associated with plasma TFPI levels, however, it remains to be further determined whether TFPI variants are associated with other coagulation factors. In this study, we carried out a large population-based study with 2,313 study subjects for blood coagulation data, including fibrinogen levels, prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). We identified significant association of TFPI variant rs10931292 (a functional promoter variant with reduced transactivation) with increased plasma fibrinogen levels (P=0.017 under a recessive model), but not with PT, APTT or TT (P>0.05). Using a large case control association study population with 4,479 CAD patients and 3,628 controls, we identified significant association between rs10931292 and CAD under a recessive model (OR = 1.23, P = 0.005). For the first time, we show that a TFPI variant is found to be significantly associated with fibrinogen levels and risk of CAD. Our finding contributes significantly to the elucidation of the genetic basis and biological pathways responsible for fibrinogen levels and development of CAD.
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