急性冠脉综合征血清MMP-3水平及其基因启动子区域5A/6A多态

目的探讨基质金属蛋白酶-3（MMP-3）血清水平及其基因启动子区域5A/6A多态性与急性冠脉综合征（ACS）的关系。方法 ACS组135例,对照组71例。测定MMP-3血清水平,并对MMP-3启动子区域基因测序,分析其5A/6A多态性。结果 ACS组中AMI亚组的MMP-3血清水平高于对照组（P〈0.01）。MMP-3基因启动子区5A/6A单核苷酸多态性（SNP）的基因型在ACS组和对照组的分布有统计学差异（P〈0.05）,在ACS组中5A等位基因频率高于对照组（P〈0.05）。ACS组5A/5A基因型血清MMP-3浓度高于5A/6A基因型血清MMP-3浓度（P〈0.05）;ACS组5A/5A＋5A/6A基因型血清MMP-3浓度高于6A/6A基因型血清MMP-3浓度（P〈0.05）。进行多因子logistic回归分析,发现吸烟、高脂血症、糖尿病、高血压为ACS的主要危险因子,5A/5A＋5A/6A基因型（OR2.11,95%CI1.23～5.11,P〈0.01）亦是ACS发病的独立危险因子。吸烟并携带5A等位基因者较不吸烟携带6A/6A者有5倍的ACS发病风险（P〈0.01）。结论 MMP-3基因启动子区域5A/6A多态性及MMP-3循环水平升高与ACS发病密切相关;MMP-3血清水平受其基因5A/6A单核苷酸多态性的影响;吸烟与MMP-3基因5A/6A多态性对ACS具有协同的影响。

Serum MMP-3 level and MMP-3 5A/6A promoter polymorphism in patients with acute coronary syndromes

Objective To investigate the association between serum matrix metalloproteinase-3 （MMP-3） concentrations and its 5A/6A promoter polymorphism in patients with acute coronary syndromes （ACS）.Methods A total of 135 ACS patients and 71 control subjects who were free of ACS symptomes were enrolled.Serum concentrations of MMP-3 were measured by enzyme linked immunosorbent assay （ELISA）.MMP-3 promoter gene was sequenced and the 5A/6A polymorphism was analyzed.Results Serum MMP-3 levels were significantly higher in AMI group than in controls（P0.01）.The distribution of MMP-3 single nucleotide polymorphism （SNP） genotype was significantly different between ACS patients and the controls （P0.05）.The 5A allele had higher frequency in ACS patients than in controls （P0.05）.The 5A allele polymorphism was strongly associated with higher serum MMP-3 levels in ACS patients.Serum MMP-3 levels were significantly higher in ACS patients with 5A/5A genotype than those with 5A/6A genotype （P0.05）.Multivariate logistic regression analysis showed that smoking,hyperlipidemia,diabetes,hypertension,as well as 5A allele polymorphism （OR 2.11,95%CI 1.23-5.11,P0.01）,were independent risk factors for ACS.Carriers of 5A allele with smoking history had a significantly increased risk （5-fold） for ACS compared with nonsmoking carriers of 6A/6A（P0.01）.Conclusion The MMP-3 5A/6A promoter polymorphism and increased MMP-3 level are significantly associated with ACS attack.The MMP-3 5A/6A promoter polymorphism exerts effects on serum MMP-3 levels.Smoking and MMP-3 5A/6A promoter polymorphism have a synergistic effect on ACS.These data suggest that MMP-3 be a useful marker for ACS,and play an important role in the induction of atherosclerosis plaque rupture.