CAJ | 학술논문

目的评价基质金属蛋白酶(mmp)基因(1、2,3、9)多态性对冠状动脉粥样斑块进展的影响.方法2005年1月至2008年12月80例在我院行2次冠状动脉造影的冠心病患者,根据冠脉粥样斑块有无进展(第2次冠脉造影任何节段冠脉病变的最小管腔直径较第一次冠脉造影减少0.4 mm者为冠脉粥样斑块有进展),将患者分为斑块进展组(n=31)和非斑块进展组(n=49).详细记录每例患者临床特征,包括冠心病易患因素等,以及检测每例患者的血脂、血糖、超敏C反应蛋白(hsCRP)等.应用PCR直接测序技术测定两组患者MMP-1、MMP-2、MMP-3和MMP-9基因启动子部位的序列,分析两组多态频率.结果斑块进展组中,女性和急性冠脉综合征(acute coronary syndrome,ACS)患者上述基因的多态比率明显高于非斑块进展组(分别为41.9%比18.4%,P<0.05和77.4%比46.3%,P<0.01);斑块进展组hs-CRP的浓度也明显高于非斑块进展组[(0.26±0.44)mg/L比(0.02±0.14)mg/L,P<0.01).多因素Logistic逐步回归分析显示:高浓度hs-CRP和ACS是冠状动脉粥样斑块进展的独立危险因素(OR为12.63,95%CI为1.45～110.29,P<0.05和OR为2.99,95%CI为1.04～8.63,P<0.05).斑块进展组中MMP-3(-1612 6A/6A)基因型和MMP3(-1612 6A)等位基因频率均显著高于非斑块进展组(87.1%比53.1%.P<0.01和93.5%比75.5%,P<0.01).MMP-1(-1607 GC)、MMP-2(-955A/C)和MMP-9(-1562C/T)的基因型和等位基因频率在斑块进展组与非斑块进展组中均无显著差异.结论女性、高浓度hs-CRP和ACS与冠状动脉粥样斑块进展明显相关,高浓度hs-CRP和ACS足冠状动脉粥样斑块进展的独立危险因素.MMP-3启动子区域5A/6A基因多态性与冠状动脉粥样硬化斑块的进展显著相关,可能是冠状动脉粥样硬化斑块的进展标志.
목적 평개기질금속단백매(mmp)기인(1、2,3、9)다태성대관상동맥죽양반괴진전적영향.방법2005년1월지2008년12월80례재아원행2차관상동맥조영적관심병환자,근거관맥죽양반괴유무진전(제2차관맥조영임하절단관맥병변적최소관강직경교제일차관맥조영감소0.4 mm자위관맥죽양반괴유진전),장환자분위반괴진전조(n=31)화비반괴진전조(n=49).상세기록매례환자림상특정,포괄관심병역환인소등,이급검측매례환자적혈지、혈당、초민C반응단백(hsCRP)등.응용PCR직접측서기술측정량조환자MMP-1、MMP-2、MMP-3화MMP-9기인계동자부위적서렬,분석량조다태빈솔.결과 반괴진전조중,녀성화급성관맥종합정(acute coronary syndrome,ACS)환자상술기인적다태비솔명현고우비반괴진전조(분별위41.9%비18.4%,P<0.05화77.4%비46.3%,P<0.01);반괴진전조hs-CRP적농도야명현고우비반괴진전조[(0.26±0.44)mg/L비(0.02±0.14)mg/L,P<0.01).다인소Logistic축보회귀분석현시:고농도hs-CRP화ACS시관상동맥죽양반괴진전적독립위험인소(OR위12.63,95%CI위1.45～110.29,P<0.05화OR위2.99,95%CI위1.04～8.63,P<0.05).반괴진전조중MMP-3(-1612 6A/6A)기인형화MMP3(-1612 6A)등위기인빈솔균현저고우비반괴진전조(87.1%비53.1%.P<0.01화93.5%비75.5%,P<0.01).MMP-1(-1607 GC)、MMP-2(-955A/C)화MMP-9(-1562C/T)적기인형화등위기인빈솔재반괴진전조여비반괴진전조중균무현저차이.결론 녀성、고농도hs-CRP화ACS여관상동맥죽양반괴진전명현상관,고농도hs-CRP화ACS족관상동맥죽양반괴진전적독립위험인소.MMP-3계동자구역5A/6A기인다태성여관상동맥죽양경화반괴적진전현저상관,가능시관상동맥죽양경화반괴적진전표지.
Objective To evaluate the influence of the gene polymorphisms of matrix metalloproteinase(mmp)-1 ,-2,-3 and -9 on coronary atherosclerotic plaque progression. Methods During the period of January 2005-December 2008, 80 patients with coronary heart disease underwent two times coronary angiography at authors' hospital. Based on the angiographic findings, the patients were classified into plaque progression group (n = 31 ) and plaque non-progression group (n = 49). Coronary atheroselerotic plaque progression was arbitrarily defined as that the minimal lumen diameter (MLD) of coronary artery showed a decrease ≥ 0.4 mm on the second coronary angiography. The detailed history and clinical examination results were collected, including serum concentrations of lipid profiling, fasting glucose and hs-CRP. Genotypings for polymorphic variances of MMP-1 (-1607 G/GG), MMP-2 (-955 A/C), MMP-3 (-1612 5A/6A ) and MMP-9 (-1562 C/T) were performed by polymerase chain reaction (PCR) and sequencing analysis in two groups.Comparison of the clinical characteristics and polymorphisms between two groups was made to assess their effects on coronary atherosclerotic plaque progression. Results More female patients and patients with acute coronary syndrome (ACS) were noted in patients with plaque progression compare to those with no progression (41.9% vs. 18.4%, P < 0.05 and 77.4% vs. 46.3%, P < 0.01, respectively).The serum hs-CRP level also significantly increased in group with plaque progression (0.26 ± 0.44 mg/L vs.0.02 ± 0.14 mg/L, P < 0.01). Multivariable logistic regression analysis revealed that serum hs-CRP concentration and ACS were independent risk factors of coronary atherosclerotic plaque progression (OR:12.63,95% CI:1.45-110.29, P < 0.05 and OR:2.99,95% CI:1.04-8.63, P < 0.05, respectively). The frequencies of 6A/6A genotype and 6A allele of MMP-3 promoter at location -1612 were significantly higher in group with plaque progression than that in group with no progression (87.1% vs. 53.1%, P < 0.01 and 93.5% vs. 75.5%, P < 0.01, respectively). However, no significant differences in the distribution of MMP-1,-2 and -9 polymorphisms existed between two groups. Conclusion ACS, feminine gender, high serum hs-CRP concentration and 5A/6A polymorphism in the MMP-3 gene promoter are closely associated with coronary atherosclerotic plaque progression. In addition, 5A/6A polymorphism of MMP-3 can be used as a marker for plaque progression.