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

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

摘要:

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。

Abstract:

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(P<0.01).The distribution of MMP-3 single nucleotide polymorphism (SNP) genotype was significantly different between ACS patients and the controls (P<0.05).The 5A allele had higher frequency in ACS patients than in controls (P<0.05).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 (P<0.05).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,P<0.01),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(P<0.01).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.