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[基质金属蛋白酶-9(MMP-9)基因启动子区C(-1562)T多态性与冠状动脉粥样硬化]

[The C(-1562)T polymorphism in the promoter of the matrix metalloproteinase-9 (MMP-9) gene and coronary atherosclerosis].

作者信息

Goracy Jarosław, Goracy Iwona, Brykczyński Mirosław, Peregud-Pogorzelska Małgorzata, Naruszewicz Marek, Ciechanowicz Andrzej

机构信息

Klinika Kardiologii Pomorskiej AM w Szczecinie.

出版信息

Pol Arch Med Wewn. 2003 Nov;110(5):1275-81.

PMID:16736997
Abstract

Atherosclerosis of coronary arteries is a main cause of ischaemic heart disease (IHD). Matrix metalloproteinases, a super-family of zink-dependent enzymes, which are involved in the pathogenesis of atherosclerosis by the activation of migration and proliferation of smooth muscle cells and by the induction of destabilization of atherosclerotic plaques. Some observations suggest that C(-1562)T polymorphism of matrix metalloproteinase-9 (MMP-9) promoter predisposes to multivessel IHD. Therefore, the aim of our study was to evaluate the association between C(-1562)T MMP-9 polymorphism and angiographically-documented coronary atheroclerosis in 110 patiens. Genomic DNA isolated from peripheral blood nuclear cells was amplified by PCR method with pair of primers flanking the polymorphic regions and subsequently MMP-9 genotypes were identified by amplicon digestion with Pac I restriction enzyme. The T(-1562) allel was idientified by gain of restriction site. There were 67 CC homozygotes and 43 carriers of T allele (41 CT + 2 TT). No differences has been found among patiens with various number of significantly stenotic (>50%) coronary arteries (group 0, 1, 2 and 3, respectlively) in genotype distribution, age, prevalance of arterial hypertension, and plasma concentrations of triglycerides, cholesterol and fibrinogen. However, in subjects younger < 50 years, the frequency of T(-1562) allele was significantly higher in IHD patients as compared with controls (group O). Results of our preliminary study suggest, that C(-1562)T MMP-9 transition is associated with premature IHD in Polish patients.

摘要

冠状动脉粥样硬化是缺血性心脏病(IHD)的主要病因。基质金属蛋白酶是一类锌依赖性酶的超家族,通过激活平滑肌细胞的迁移和增殖以及诱导动脉粥样硬化斑块的不稳定参与动脉粥样硬化的发病机制。一些观察结果表明,基质金属蛋白酶-9(MMP-9)启动子的C(-1562)T多态性易导致多支血管IHD。因此,我们研究的目的是评估110例患者中C(-1562)T MMP-9多态性与血管造影记录的冠状动脉粥样硬化之间的关联。从外周血细胞核细胞中分离的基因组DNA通过PCR方法用位于多态性区域两侧的引物对进行扩增,随后通过用Pac I限制性酶消化扩增子来鉴定MMP-9基因型。通过限制位点的获得鉴定出T(-1562)等位基因。有67例CC纯合子和43例T等位基因携带者(41例CT + 2例TT)。在具有不同数量显著狭窄(>50%)冠状动脉的患者(分别为0、1、2和3组)中,在基因型分布、年龄、动脉高血压患病率以及甘油三酯、胆固醇和纤维蛋白原的血浆浓度方面未发现差异。然而,在年龄小于50岁的受试者中,IHD患者中T(-1562)等位基因的频率与对照组(O组)相比显著更高。我们初步研究的结果表明,C(-1562)T MMP-9转变与波兰患者的早发性IHD相关。

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