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凝血酶激活的纤溶抑制物基因多态性与静脉血栓形成风险的关联:一项荟萃分析。

Association between thrombin-activatable fibrinolysis inhibitor gene polymorphisms and venous thrombosis risk: a meta-analysis.

作者信息

Wang Wei, Ma He, Lu Lili, Sun Guixiang, Liu Dang, Zhou Yunti, Tong Yue, Lu Zhaojun

机构信息

aDepartment of Public HealthbDepartment of GastroenterologycDepartment of General Practice, Xuzhou Medical College, Xuzhou, Jiangsu, China*Wei Wang and He Ma have contributed equally to the manuscript.

出版信息

Blood Coagul Fibrinolysis. 2016 Jun;27(4):419-30. doi: 10.1097/MBC.0000000000000475.

Abstract

Thrombin-activatable fibrinolysis inhibitor (TAFI) is an important antifibrinolytic factor that has been shown in increased concentrations to be associated with an increased risk for venous thrombosis. However, the effect of TAFI gene polymorphisms on the risk of venous thrombosis remains debatable. The aim of the current study was to evaluate the association of three single nucleotide polymorphisms: 505G>A (rs3742264), 1040 C>T (rs1926447) and -438G>A (rs2146881) with venous thrombosis risk using a meta-analysis. A systematic literature search for eligible studies published before 20 January 2015 was conducted in PubMed, EMBASE, Web of Science, WanFang database and Chinese National Knowledge Infrastructure. We assessed the possible association by pooled odds ratio and its 95% confidence interval. A total of 14 independent case-control studies including 2970 cases and 3049 controls were enrolled in the final meta-analysis. A significant reduction of venous thrombosis risk in the 505G>A polymorphism was observed under allele comparison, homozygote comparison and recessive models, but opposite results were seen in Asians. Likewise, there was a significant decreased susceptibility to venous thrombosis in the 1040C>T polymorphism in homozygote comparison and recessive models. In the subgroup analysis, the nonvenous thromboembolism disease group showed a significantly increased venous thrombosis risk. Pooled estimates did not show evidence of association between -438G>A and venous thrombosis risk in any genetic model. This meta-analysis suggested that although the -438G>T polymorphism is not correlated with venous thrombosis risk in all models, a trend toward reduced risk still could be observed. The A allele and AA genotype of 505G>A in whites and the TT genotype of 1040C>T were significantly associated with a decreased risk of venous thrombosis, except in the non-venous thromboembolism group.

摘要

凝血酶激活的纤维蛋白溶解抑制剂(TAFI)是一种重要的抗纤维蛋白溶解因子,研究表明其浓度升高与静脉血栓形成风险增加相关。然而,TAFI基因多态性对静脉血栓形成风险的影响仍存在争议。本研究的目的是通过荟萃分析评估三个单核苷酸多态性:505G>A(rs3742264)、1040C>T(rs1926447)和-438G>A(rs2146881)与静脉血栓形成风险的关联。在PubMed、EMBASE、Web of Science、万方数据库和中国知网中对2015年1月20日前发表的符合条件的研究进行了系统的文献检索。我们通过合并比值比及其95%置信区间评估可能的关联。最终的荟萃分析纳入了14项独立的病例对照研究,包括2970例病例和3049例对照。在等位基因比较、纯合子比较和隐性模型下,观察到505G>A多态性的静脉血栓形成风险显著降低,但在亚洲人群中结果相反。同样,在纯合子比较和隐性模型下,1040C>T多态性对静脉血栓形成的易感性显著降低。在亚组分析中,非静脉血栓栓塞疾病组的静脉血栓形成风险显著增加。在任何遗传模型中,合并估计均未显示-438G>A与静脉血栓形成风险之间存在关联的证据。这项荟萃分析表明,虽然-438G>T多态性在所有模型中均与静脉血栓形成风险无关,但仍可观察到风险降低的趋势。除非静脉血栓栓塞组外,白种人中505G>A的A等位基因和AA基因型以及1040C>T的TT基因型与静脉血栓形成风险降低显著相关。

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