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Study On The Association Of The Gene Polymorphism Of Thrombin Activatable Fibrinolysis Inhibitor With Coronary Atherosclerotic Heart Disease

Posted on:2009-02-01Degree:MasterType:Thesis
Country:ChinaCandidate:L L WangFull Text:PDF
GTID:2144360245495412Subject:Clinical Laboratory Science
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Objectives: The present study was carried out as a pilot study to examine the antigen and the activity of TAFI in patients with coronary heart disease, and investigate the association of thrombin activatable fibrinolysis inhibitor (TAFI) and its encoding gene CPB2 polymorphism among patients with coronary atherosclerotic heart disease (CAD) . In the meantime, to analyze CAD is related to the changes of coagulative and fibrinolytic function. With the help of relevant documents, further to analyze the clinical significances of TAFI in the treatment of CAD.Methods: CPB2 gene (Thr325Ile) polymorphism were typed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients of acute myocardial infarction (n=100), acute angina pectoris(n=110) and a control group (n=190). The antigen (Ag) and the activity (Act) of TAFI ,t-PA and PAI-1 were determined by enzyme link immunosorbent assay(ELISA) and chromogenic assay , respectively . In addition, D-dimer and Fg were determined by immunoturbidimetry (ITM) and Clauss assay, independently. Moreover, the association of Thr325Ile gene polymorphism , TAFI ,t-PA , PAI-1, D-dimer and Fg with CAD were also analyzed.Results: Plasma TAFI Act and TAFI Ag were 51.4±9.3μg/ml, 145.6±33.5 % in acute myocardial infarction group, 44.6±8.4μg/ml, 128.3±28.7 % in acute angina pectoris group, both being significantly higher than those of control group (TAFI Act 26.4±6.5μg/ml,TAFIAg79.2±25.8%),respectively(F=12.92,p<0.0001;F=28.79, p<0.0001); The genotypes(Thr/Thr, Thr/Ile, Ile/Ile)frequencies of Thr325Ile were 32 (32%), 53 (53%), 15 (15%); 31 (28.2%), 58 (52.7%), 21 (19%) and 64 (33.6%), 92 (48.4%), 34 (17.8%) and allelic frequencies (C and T) were 117 (58.5%), 83(41.5%); 120(54.5%), 100(45.5%)and 220(57.9%), 160(42.1%), in acute myocardial infarction group, acute angina pectoris group and control group respectively.χ~2 analysis showed no significant difference in the Thr325Ile polymorphism distributions (χ~2=1.587 7, P=0.811 0;χ~2 =0.844 0, P=0.655 7); Genotype and alleles distribution were in accordance with Hardy-Weinberg equilibrium. In additional, at the 325 position, the TAFI antigen of the Thr325Thr was higher than that of the other genotypes (Thr325Ile and Ile325Ile), there was significance between the TAFI antigen of the Thr325Thr and the others (p<0.05), and no statistical significance between the TAFI antigen of the Thr325Ile and Ile325Ile(p>0.05). No significant correlation was found between TAFI Act and gene (Thr325Ile) polymorphism. Compared with control group ,t-PA Act of CAD was diminished obviously, but t-PA Ag, PAI-1 Ag and PAI-1 Act were elevated significantly in patients with CAD (p<0.05) . Otherwise, the levels of D-dimer and Fg in CAD were higher significantly than those of the control group(p<0.01).Conclusion: TAFI defines a novel molecular connection between blood coagulation and fibrinolysis, it can depress the activity of fibrinolysis and have an effect on the risk of coronary artery thrombophilia; there was obvious effect on TAFI antigen levels in the gene polymorphism at amino acid Thr325Ile, but the Thr325Ile polymorphism was not associated with coronary heart disease. Simultaneously studies on TAFI and its inhibitor may be able to open up a new way for the development of thrombolytic drug and the treatment of CAD.
Keywords/Search Tags:thrombin activatable fibrinolysis inhibitor (TAFI), gene single nucleotide polymorphism(SNP), coronary atherosclerotic heart disease (CAD), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
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