基质金属蛋白酶-9及血小板膜糖蛋白Ⅵ基因多态性与急性冠状动脉综合征的相关性研究

Association of matrix metalloproteinase-9 and platelet membrane glycoprotein Ⅵ polymorphisms with acute coronary syndrome

目的探讨金属蛋白酶(MMP-9)血浆水平、基因多态性与血小板膜糖蛋白Ⅵ(GPⅥ)基因多态性在急性冠状动脉综合征(ACS)发病中的作用及其相关性。方法对179例经冠状动脉造影及临床表现证实为ACS的患者与164例经冠状动脉造影证实无冠状动脉病变的对照者进行研究,采用ELISA法测定血浆MMP-9水平;Clauss法测定纤维蛋白原(Fib)水平;采用多聚酶链反应-限制性内切酶片断长度多态性(PCR-RFLP)分析MMP-9基因中C-1562T、G5564A和GPⅥT13254C、FibBβ链-148C/T基因多态性。结果ACS组血浆MMP-9和Fib水平明显高于对照组,P<0·001;急性心肌梗死组的血浆Fib水平高于不稳定性心绞痛组,P<0·05。ACS组与对照组比较,MMP-9/C-1562T、MMP-9/G5564A和GPⅥT13254C、FibBβ链-148C/T基因型与等位基因频率分布差异无统计学意义。当FibBβ链出现T等位基因时,血浆Fib水平明显升高,P<0·05。显示MMP-9及Fib与ACS发病呈明显正相关(r=0·289,P<0·01)。结论MMP-9及Fib是ACS发病的独立危险因素,FibBβ链T等位基因与血浆Fib水平升高有关,MMP-9C-1562T、G5564A和GPⅥT13254C、FibBβ链-148C/T等位基因频率分布在ACS组对照组之间差异无统计学意义。

Objective To investigate serum level and gene polymorphisms of matrix metalloproteinase 9（ MMP-9 ） , and platelet glycoprotein Ⅵ（GPⅥ） in patients with acute coronary syndrome （ACS）. Methods In a prospective study of 179 patients with documented ACS and 164 controls, we measured baseline serum MMP-9 levels using ELISA and determined the MMP-9/C-1562T and MMP-9/G5564A genotypes using PCR-restriction fragment length polymorphism. Fib serum level was measured by Clauss assay. We also analyzed the Fib/Bβ-148C/T and GPⅥ/T13254C polymorphisms. Results Serum levels of MMP-9 and Fib in ACS patients were significantly higher than in controls （ P 〈0. 001 ） , and serum level of Fib in the acute myocardial infarction group was higher than in patients with unstable angina （ P 〈 0. 05）. No significant difference between ACS patients and controls was found in frequencies of MMP-9/C-1562T, MMP-9/G5564A, Fib/Bβ-148C/T, and GPⅥ/T13254C genotypos and alleles （P 〉 0. 05）. The T allele of the Fib/Bβ-148T polymorphism was associated with increased plasma Fib level （P 〈 0.05 ）. There was a strong positive correlation between serum level of MMP-9 and Fib （r = 0. 289 ,P 〈0.01 ）. Conclusion Serum levels of MMP-9 and Fib were independent risk factors of ACS. There was an obvious relationship between the Bβ-148C/T mutation and high Fib level. No significant difference between controls and ACS patients was found in the frequencies of MMP-9 C-1562T and G5564A,Fib Bβ-148C/T and GPⅥ T13254C genotypes and alleles （ P 〉 0. 05 ）.