凝血酶激活的纤溶抑制物及其编码基因多态性与冠心病的相关性研究

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目的研究凝血酶激活的纤溶抑制物(TAFI)及其编码基因多态性与冠心病(CHD)之间的相关性。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)对136例冠心病患者和85名健康对照者的TAFI编码基因Thr325Ile和Thr147Ala的基因多态性进行分析,同时采用酶联免疫吸附试验双抗体夹心法对所有受试者血浆TAFI的抗原及活性水平进行检测,探讨TAFI及其编码基因的基因多态性与CHD的关系。结果健康对照组和CHD组血浆TAFI的抗原与活性水平分别为(72.50±33.95)%、(21.75±13.79)μg/ml和(185.21±89.82)%、(91.29±43.48)μg/ml,两组之间的差异有统计学意义(P<0.01)。在健康对照组和CHD组TAFI编码基因的基因多态性分布中,Thr325Ile编码基因的3种基因型和Thr147Ala编码基因的3种基因型两组之间基因型及等位基因的多态性分布频率差异无统计学意义(P>0.05)。在Thr325Ile编码基因的3种基因型中,Thr325Thr基因型血浆TAFI的抗原水平明显高于其他两种基因型(Thr325Ile和Ile325Ile),差异有统计学意义(Ρ<0.01),而后两种基因型之间差异无统计学意义(P>0.05);Ile325Ile基因型血浆TAFI的活性水平较其他两种基因型(Thr325Thr和Thr325Ile)低,差异有统计学意义(Ρ<0.01),而后两者之间的差异无统计学意义(P>0.05);在Thr147Ala编码基因的3种基因型(Ala147Ala、Ala147Thr和Thr147Thr)之间,血浆TAFI的抗原与活性水平的差异无统计学意义(P>0.05)。结论 TAFI可能是CHD的危险因子;TAFI编码基因Thr325Ile的基因多态性对血浆TAFI的抗原与活性水平有一定的影响,但TAFI的两种编码基因Thr325Ile与Ala147Thr的基因多态性与CHD的发生并无明显的相关性。 Objective To investigate the correlation between thrombin-activated fibrinolysis inhibitor (TAFI) and its coding gene polymorphism and coronary heart disease (CHD). Methods The gene polymorphisms of Thr325Ile and Thr147Ala in TAFI gene of 136 CHD patients and 85 healthy controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Meanwhile, the antigen and activity of plasma TAFI in all subjects were detected by enzyme-linked immunosorbent assay (ELISA) double antibody sandwich method. The relationship between gene polymorphism of TAFI and its coding gene and CHD was explored. Results The plasma levels of TAFI in healthy controls and CHD patients were (72.50 ± 33.95)%, (21.75 ± 13.79) μg / ml and (185.21 ± 89.82)%, (91.29 ± 43.48) μg / The difference was statistically significant (P <0.01). In the distribution of TAFI-encoding genes in healthy control group and CHD group, the genotype and allele distributions of the three genotypes of Thr325Ile and Thr147Ala were No significant difference in frequency (P> 0.05). Among the three genotypes of Thr325Ile gene, the plasma level of TAFI in Thr325Thr genotype was significantly higher than that in the other two genotypes (Thr325Ile and Ile325Ile) (P <0.01), while the latter two genotypes (P> 0.05). The level of plasma TAFI in Ile325Ile genotype was lower than that of the other two genotypes (Thr325Thr and Thr325Ile) (P <0.01), and the difference between the latter two was not statistically significant (P> 0.05). There was no significant difference in the antigen and activity level of plasma TAFI between the three genotypes of Thr147Ala (Ala147Ala, Ala147Thr and Thr147Thr) (P> 0.05). Conclusions TAFI may be a risk factor for CHD. The polymorphism of Thr325Ile gene in TAFI gene may have some influence on the antigen and activity level of plasma TAFI. However, the genetic polymorphism of Thr325Ile and Ala147Thr between TAFI gene and CHD There is no obvious correlation.
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