凝血酶激活的纤溶抑制物及其编码基因CPB2(Thr325Ile)多态性与心肌梗死关系的研究

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目的探讨凝血酶激活的纤溶抑制物(TAFI)及其编码基因单核苷酸多态性与心肌梗死的关系。方法应用聚合酶链反应-限制性内切酶片段长度多态性分析技术(PCR-RFLP)检测了100例心肌梗死(MI)患者和90名正常对照者的 CPB2基因多态性,同时应用发色底物法和 ELISA 法分别测定了 TAFI 的活性及抗原,并进一步分析了基因多态性与 TAFI 的活性及抗原之间的关系。结果 MI 组 TAFI 的活性及抗原[TAFI Act(51.4±9.3)μg/ml,TAFI Ag(145.6±33.5)%]均较对照组[TAFI Act(25.7±5.6)μg/ml,TAFI Ag(76.5±24.8)%]显著增高(t=22.927 2,P<0.000 1;t=16.012 7,P<0.000 1);CPB2基因的3种基因型(Thr325Thr、Thr325Ile、Ile325Ile)频率在 MI 组和对照组分别为32例(32%)、53例(53%)、15例(15%)和31例(34.4%)、49例(54.4%)、10例(11.2%),等位基因 C、T 频率在 MI 组和对照组分别为117例(58.5%)、83例(41.5%)和111例(61.7%)、69例(38.3%)两组之间基因型及等位基因频率分布差异无统计学意义(基因型频率分布 x~2=0.648 2,P=0.723 2;等位基因频率分布 x~2=0.395 8,P=0.529 2),且均符合 Hardy-Weinberg 平衡定律;在心梗组和对照组不同的基因型对 TAFI 活性没有影响(心梗组 F=0.24,P=0.784 7;对照组 F=0.80,P=0.453 5),而对 TAFI 抗原含量的影响,则以 Thr325Thr 基因型者血浆 TAFI 抗原浓度最高,TIle325Ile 型最低,Thr325Ile 型介于两者之间(F=36.33,P<0.000 1;F=6.76,P<0.000 1)。结论TAFI 具有抑制纤溶的作用,可能是心肌梗死的危险因子。但 CPB2基因(Thr325Ile)的基因多态性与心肌梗死没有明显关系。 Objective To investigate the relationship between thrombin-activated fibrinolysis inhibitor (TAFI) and its single nucleotide polymorphisms (SNPs) and myocardial infarction. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect CPB2 gene polymorphism in 100 patients with myocardial infarction (MI) and 90 normal controls. At the same time, The activity and antigen of TAFI were determined by colorimetric assay and ELISA respectively. The relationship between gene polymorphism and TAFI activity and antigen was further analyzed. Results Compared with the control group [TAFI Act (25.7 ± 5.6) μg / ml and TAFI Ag (76.5 ±)], TAFI activity and antigen in the MI group were significantly higher than those in the TAFI Act group (TAFI Act 51.4 ± 9.3 μg / ml and TAFI Ag 145.6 ± 33.5% (Thr325Thr, Thr325Ile and Ile325Ile) in the MI group and the control group respectively (t = 22.927 2, P <0.000 1; t = 16.012 7, P <0.0001) There were 32 cases (32%), 53 cases (53%), 15 cases (15%) and 31 cases (34.4%), 49 cases (54.4%) and 10 cases (11.2% In the MI group and the control group, there were 117 cases (58.5%), 83 cases (41.5%), 111 cases (61.7%) and 69 cases (38.3% (Genotype frequency distribution x ~ 2 = 0.648 2, P = 0.723 2; allele frequency distribution x ~ 2 = 0.395 8, P = 0.529 2), and all were in accordance with the Hardy-Weinberg equilibrium law; The genotypes of TAFI did not affect the activity of TAFI in the control group (F = 0.24, P = 0.784 7, F = 0.80, P = 0.453 5 in the MI group), while the effect on the TAFI antigen content was based on the Thr325Thr genotype The highest plasma TAFI antigen concentration, TIle325Ile type lowest, Thr325Ile type between the two (F = 36.33, P <0.0001; F = 6. 76, P <0.000 1). Conclusions TAFI can inhibit fibrinolysis and may be a risk factor for myocardial infarction. However, the gene polymorphism of CPB2 gene (Thr325Ile) has no obvious relationship with myocardial infarction.
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