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目的研究汉族人血浆中凝血酶活化的纤溶抑制物水平及编码区的基因多态性分布特征与冠状动脉粥样硬化性心脏病之间的相关性。方法应用 ELISA 及发色底物法分别检测了126例冠状动脉粥样硬化性心脏病患者和45名健康对照组血浆中的 TAFI 抗原及活性水平,同时应用PCR 结合限制性片段长度多态性技术研究了浙江地区156名汉族健康人与126例冠状动脉粥样硬化性心脏病患者 TAFI 基因编码区 Thr325Ile、Thr147Ala 多态性分布特点,并分析这两个多态性位点与冠状动脉粥样硬化性心脏病之间的关系。结果急性心肌梗死组患者血浆中 TAFI 抗原与活性水平分别为(106.82±24.51)%和(6.32±1.58)μg/ml,心绞痛组患者血浆中 TAFI 抗原与活性水平分别为(100.73±30.39)%和(6.92±1.78)μg/ml,经方差分析,二者之间及其与对照组之间的差异无统计学意义(P>0.05);在浙江汉族人群中 TAFI Thr325Ile 的基因多态性分布中 Thr325Thr(1040C/C)占0.667 0,Thr325Ile(1040C/T)占0.262 0,Ile325Ile(1040T/T)占0.071 0;104 0位 C 与 T 等位基因频率的分别为0.798 0与0.202 0,TAFI Thr147Ala 的基因型分布中 Ala147Ala(505G/G)为0.603 0,Ala 147 Thr(505G/A)为0.278 0,Thr147Thr(505A/A)为0.119 0,505位 G 与 A 等位基因频率分别为0.742 0与0.258 0,冠状动脉粥样硬化性心脏病组与对照组中基因型的分布频率和等位基因频率之间的差异也无统计学意义(P>0.05);另外,在 Thr325Ile 基因多态性中,纯合子 Thr325Thr(1040C/C)者血浆 TAFI 抗原水平为(114.89±22.53)%,较其他两型(1040C/T、1040T/T)高,差异有统计学意义(P<0.05),而后两型之间差异无统计学意义(P>0.05);纯合子 Ile325Ile(1040T/T)的 TAFI 活性为(3.08±3.63)μg/ml,较其他两型(1040C/T、1040T/T)低,差异有统计学意义(P<0.05),而后两者之问的差异无统计学意义(P>0.05);而 Thr147Thr(505AZA)、Thr147Ala(505C/T)、AIa147Ala(505G/C)3种基因型血浆中 TAFI 水平(抗原与活性)之间的差异均无统计学意义(P>0.05)。结论TAFI 编码区 Thr325Ile 基因多态性对血浆中 TAFI 抗原与活性水平有明显的影响,但 TAFI Ala147Thr与 Thr325Ile 两种基因多态性与冠状动脉粥样硬化性心脏病的发生无明显的相关性。
Objective To investigate the relationship between plasma thromboplastin-dependent fibrinolysis inhibitors and gene polymorphism in coronary heart disease (CHD) and coronary heart disease (CHD) in Chinese Han population. Methods The plasma levels of TAFI antigen and activity in 126 patients with coronary atherosclerotic heart disease and 45 healthy controls were detected by ELISA and chromogenic substrate method respectively. PCR and restriction fragment length polymorphism To investigate the distribution of Thr325Ile and Thr147Ala polymorphisms in the coding region of TAFI in 156 Han healthy people and 126 patients with coronary atherosclerotic heart disease in Zhejiang province and to analyze the relationship between these two polymorphisms and coronary atherosclerosis The relationship between sex heart disease. Results The levels of TAFI antigen and activity in plasma of patients with acute myocardial infarction were (106.82 ± 24.51)% and (6.32 ± 1.58) μg / ml, respectively. The levels of TAFI antigen and activity in plasma of patients with angina pectoris were (100.73 ± 30.39)% and (6.92 ± 1.78) μg / ml, respectively. There was no significant difference between them and the control group (P> 0.05) by ANOVA. In the distribution of TAFI Thr325Ile polymorphism in Zhejiang Han population Thr325Thr (1040C / C) accounted for 0.667 0, Thr325Ile (1040C / T) accounted for 0.262 0, Ile325Ile (1040T / T) accounted for 0.071 0, and the frequencies of allele C at 104 0 were 0.798 0 and 0.202 0 respectively. TAFI The genotype distribution of Thr147Ala was 0.603 0 for Ala147Ala (505G / G), 0.278 0 for Ala 147 Thr (505G / A) and 0.119 for Thr147Thr (505A / A). The frequencies of G and A alleles were 0.742 0 and 0.258 0. There was also no significant difference in the frequencies of genotype distribution and allele between coronary heart disease group and control group (P> 0.05). In addition, in the Thr325Ile gene polymorphism (114.89 ± 22.53)% of the homozygous Thr325Thr (1040C / C) were higher than those of the other two types (1040C / T and 1040T / T ), The difference was statistically significant (P <0.05), while there was no significant difference between the latter two groups (P> 0.05). The TAFI activity of homozygous Ile325Ile (1040T / T) was (3.08 ± 3.63) μg / ml (P <0.05), but there was no significant difference between the latter two groups (P> 0.05); while Thr147Thr (505AZA), There were no significant differences in TAFI levels (antigen and activity) between plasma Thr147Ala (505C / T) and AIa147Ala (505G / C) genotypes (P> 0.05). Conclusion The Thr325Ile polymorphism in TAFI coding region has a significant effect on plasma TAFI antigen and activity levels. However, there is no significant correlation between TAFI Ala147Thr and Thr325Ile polymorphisms and coronary atherosclerotic heart disease.