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  • 杨虹,张戟,李伟明,等.MMP-3基因启动子区域5A/6A多态性与急性冠脉综合征的关联研究[J].同济大学学报(医学版),2010,31(3):32-37.    [点击复制]
  • YANG Hong,ZHANG Ji,LI Wei-ming,et al.Association between promoter 5A/6A polymorphism of MMP-3 gene and the occurrence of acute coronary syndromes[J].同济大学学报(医学版),2010,31(3):32-37.   [点击复制]
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MMP-3基因启动子区域5A/6A多态性与急性冠脉综合征的关联研究
杨虹1,张戟2,李伟明2,魏毅东2,沈建颖2,王勇2
0
()
摘要:
目的探讨基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)基因启动子区域5A/6A多态性与急性冠脉综合征(acute coronary syndromes,ACS)的关系。方法ACS组270例,对照组258例。对MMP-3启动子区域基因测序,并分析5A/6A多态性与血清MMP-3水平的关系。结果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纽(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纽5~5A+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)。进行多因素Logistic回归分析,发现吸烟、高脂血症、糖尿病、高血压为ACS的主要危险因素,5A/5A+5A/6A基因型(OR=2.11,95%CI1.23-5.11,P〈0.01)及血清MMP-3水平〉35μg/L(OR=1.61,95%CI1.47-2.16,P〈0.05)亦是ACS发病的独立危险因素。结论MMP-3基因启动子区域5A/6A多态性与急性冠脉综合征发病明显相关:MMP-3血清水平升高与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。本研究提示MMP-3对动脉粥样硬化斑块的破裂具有重要的作用,MMP-3可作为ACS辅助诊断的心脏标记物。
关键词:  基质金属蛋白酶-3  基因多态性  急性冠脉综合征
DOI:10.3969/j. i s sn1008 -0392.2010.03.008
投稿时间:2010-03-27
基金项目:
Association between promoter 5A/6A polymorphism of MMP-3 gene and the occurrence of acute coronary syndromes
YANG Hong1,ZHANG Ji2,LI Wei-ming2,WEI Yi-dong2,SHEN Jian-ying2,WANG yong2
()
Abstract:
Objective To study the association between serum matrix metalloproteinase-3 (MMP-3) concentrations and its promoter 5A/6A polymorphism in patients with acute coronary syndromes(ACS). Methods Two hundred and seventy ACS patients and 258 control subjects were enrolled in this study. Serum concentrations of MMP-3 were measured by enzyme linked immunoadsorbent assay (ELISA). MMP-3 promoter gene containing 5A/6A polymorphism was amplified by polymerase chain reaction (PCR). PCR products were digested by restricted fragment length polymorphism (RFLP) and then separated by electrophoresis on agarose gel. Results The distribution of MMP-3 promoter 5A/6A SNP genotype was significantly different between ACS patients and the controls (P〈 0.05). 5A allele frequency in ACS patients was significantly higher than that in controls (P〈0.05). Serum MMP-3 levels were significantly higher in 5A/SA genotype than that in 5A/6A genotype of ACS. The number of 5A allele polym0rphism was strongly associated with higher serum MMP-3 levels when compared with 6A/6A genotype in ACS (P〈0.05). Multiple logistic regression analysis showed that the polymorphism of 5A allele (OR=2.11, 95%CI 1.23-5.11, P〈0.01) and a high level (greater than 35μg/L )of serum MMP-3 (OR=1.61, 95%CI 1.47-2.16, P〈0.05)have absolute higher risk for ACS. Of course, hypertension, diabetes, hyperlipidemia and a history of smoking, were also independent risk factors for ACS events. Conclusion The MMP-3 promoter 5A/6A polymorphism is significantly associated with ACS events. High level of MMP-3 in serum has be affected by 5A/6A SNP and is correlated with ACS. The results suggest that the level of MMP-3 in serum maybe a useful marker for ACS and it might play an important role in the induction of disruption of atherosclerosis plaque.
Key words:  matrix metalloproteinase-3  genetic polymorphism  acute coronary syndromes

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