基质金属蛋白酶-3血浆水平及其启动子基因5A/6A多态性与冠心病关系的研究

目的　探讨基质金属蛋白酶 3( MMP 3)血浆水平及其启动子基因 5 A/ 6 A多态性与冠状动脉粥样硬化性心脏病 (冠心病 )的关系。方法　冠心病组 137名患者经冠状动脉造影确诊为冠心病 ,根据 WHO标准分为急性心肌梗死 ( AMI)组、不稳定型心绞痛 ( U AP)组和稳定型心绞痛 ( SA)组 ;对照组 10 6例经冠状动脉造影证实无冠状动脉狭窄病变。以酶联免疫吸附法 ( EL ISA)测定 MMP 3血浆水平。聚合酶链反应( PCR)法扩增 MMP 3启动子区域 ,酶切法及琼胶电泳法对 MMP 3启动子基因 5 A/ 6 A多态性进行分析。结果　冠心病组与对照组 MMP 3基因型分布差异无显著性。AMI组与对照组 MMP 3基因型分布差异无显著性。 AMI组血浆 MMP 3水平显著高于对照组、U AP组和 SA组〔分别为 ( 5 6 .815± 38.932 )μg/ L、( 39.14 9± 2 4 .15 5 ) μg/ L、( 4 1.6 4 0± 2 9.180 ) μg/ L 及 ( 33.336± 2 0 .75 5 ) μg/ L;P<0 .0 1、P<0 .0 5、P<0 .0 1〕。对照组、UAP组、SA组三者 MMP 3水平差异无显著性。不同冠状动脉病变支数之间血浆 MMP 3水平差异无显著性。不同基因型之间血浆 MMP 3水平差异无显著性。结论　 MMP 3启动子基因 5 A/ 6 A多态性与冠心病、AMI危险无明显相关。患者 MMP 3循环水平升高与 AMI密切相关 ,与冠状动脉病变

Association between serum matrix metalloproteinase-3 concentration and the promoter 5A/6A polymorphism in patients with coronary heart disease

OBJECTIVE: To investigate the association between serum matrix metalloproteinase-3(MMP-3) concentrations and the promoter 5A/6A polymorphism in patients with coronary heart disease (CHD). METHODS: The study enrolled 137 CHD patients and 106 control subjects without CHD. The diagnosis of both groups were confirmed by coronary artery angiography. One hundred and thirty-seven CHD patients were divided into acute myocardial infarction (AMI)group, unstable angina pectoris (UAP) group and stable angina (SA) group according to World Health Organization criteria. Serum concentration of MMP-3 was measured by enzyme linked immunoadsorbent assay (ELISA). MMP-3 promoter gene containing the 5A/6A polymorphism was amplified by polymerase chain reaction (PCR). PCR products were digested by Tth111 I and then were separated by electrophoresis on agarose gel. RESULTS: The distribution of MMP-3 genotype was not significantly different between CHD patients and controls, so was it between AMI patients and controls. Serum MMP-3 level was significantly higher in AMI group than controls, UAP group and SA group (56.815+/-38.932)microg/L, (39.149+/-24.155)microg/L, (41.640+/-29.180)microg/L, (33.336+/-20.755)microg/L; P<0.01, P<0.05, P<0.01). Serum MMP-3 levels were not significantly different among genotypes and among controls, UAP and SA groups. No significantly differences in serum MMP-3 levels were found among patients with different numbers of coronary arteries that were involved in CHD. CONCLUSION: No marked association could be found between 5A/6A polymorphism in MMP-3 gene and risk of CHD and AMI. Higher serum level of MMP-3 is strong associated with AMI, while not with number of coronary arteries that are involved in CHD. These data suggest that MMP-3 is a useful marker for AMI, and it might play an important role in the induction of disruption of atherosclerosis plaque.