金属基质蛋白酶2基因多态性对急性冠脉综合征的患者预后的影响

发布时间：2018-05-05 07:23

本文选题：金属基质蛋白酶2 + 急性冠脉综合征　；参考：《大连医科大学》2016年硕士论文

【摘要】：研究背景和研究目的:金属基质蛋白酶是一类在降解细胞外基质过程中起重要调节作用的内源性酶家族,具有锌依赖性。金属基质蛋白酶2(matrix metalloproteinases,MMP2)是其家族中的一种,又名明胶酶A,在病理状态下参与了动脉粥样硬化斑块的形成、斑块不稳定、冠脉血管的再狭窄、高血压、心室重塑、心力衰竭等过程。且已有研究发现MMP2-1306C/T的基因多态性通过转录水平的调节影响MMP2水平的表达进而引起患冠心病及急性冠脉综合征(acute coronary syndrome,ACS)的风险增加。本研究主要通过对ACS患者MMP2-1306C/T基因位点进行检测获得分型,并探讨此位点的多态性对ACS患者冠脉血管狭窄病变支数及其不良预后有无影响。研究对象及研究方法:收集在大连医科大学附属第一医院心脏急重症科和冠心病一科2013年3月至11月期间符合ACS诊断的住院患者302例,对其进行基因检测得到基因分型。详细收集患者的临床资料:化验结果、心脏彩超(左室内径及射血分数)、冠脉造影结果,并对患者进行临床随访至少一年,随访的主要终点事件是联合终点事件,即死亡、再发心绞痛、心肌梗死、心力衰竭、心律失常的复合终点;次要终点是在随访期间发生的死亡、复发心绞痛、再梗、心力衰竭、心律失常。除去在基因检测过程中检测失败的4例和失访的患者60例,最终入选238例。对其进行基因多态性分析并评估MMP2-1306C/T基因多态性对其预后有无影响。研究结果:1.基因型分布:238例入选的患者中,其中CC组患者共196例占82.4%,CT组患者共40例占16.8%,TT组患者共2例占0.8%,C等位基因的频率为90.8%,T等位基因的频率为9.2%。2.冠状动脉狭窄病变支数的比较:单、双、多支血管狭窄病变的比例在CC组和CT/TT组两组内均呈现逐渐减少的趋势,但在两组间单支57.8%vs 56.2%、双支30.5%vs 31.3%、三支11.7%vs 12.5%,差异均无统计学意义。3.临床不良预后的比较:对患者随访23.2±1.5个月,接近一半的患者发生了联合终点事件,其中再发心绞痛的患者所占的比例最高,在CC组占44.9%,CT/TT组占23.8%,其次是心力衰竭,死亡、再梗、心律失常所占的比例则较低。CC组与CT/TT组相比再发心绞痛的频率明显增加,P为0.006,具有显著差异性。联合终点事件发生率及死亡、再梗、心律失常、心力衰竭等单个事件的发生率的差异性均无统计学意义。其中CC基因型4例发生了再次心肌梗死的患者中有3例实行了PCI术,CT/TT基因型实行PCI术的患者中无一例发生再次心肌梗死。4.院外药物服用情况比较:其中阿司匹林和他汀类药物的服用率较高,在两组间均达到了80%以上。β受体阻滞剂在CC组的服用率为72.96%,CT/TT组为85.71%高于CC组。氯吡格雷、ACEI/ARB的服用率稍低。但药物在两组间比较差异均未有统计学意义5.将再发心绞痛作为因变量,年龄、性别、是否心梗、吸烟、饮酒、高血压、糖尿病、血脂水平、空腹血糖、介入治疗、住院期间服用阿司匹林、氯吡格雷、ACEI/ARB、β受体阻滞、他汀类药物及院外继续服用这些药物等结果如下作为自变量,行二分类Logistic回归分析,结果显示甘油三脂的含量、高密度脂蛋白的含量、空腹血糖的水平、AMI、MMP2-1306CC对再发心绞痛呈现相关性。结论:1.ACS患者中MMP2-1306C/T的基因表型多为CC型,CC基因型和C等位基因的频率显著高于CT/TT基因型和T等位基因的频率,与以往国内外研究一致。2.MMP2-1306CC基因型的患者复发心绞痛频率增加,CC基因型是ACS患者发生复发心绞痛的危险因素,表明CC基因型可能增加了AS斑块的不稳定性,CC基因型PCI术后再发心肌梗死的概率可能也会增加。但该基因型对患者心室重塑的影响未发现有明确关联。3.不同MMP2-1306C/T基因表型的ACS患者冠脉血管狭窄病变支数无明显差异。4.MMP2-1306CC、甘油三脂水平增高、高密度脂蛋白水平降低以及心肌梗死是ACS患者发生复发心绞痛的危险因素,空腹血糖水平也是复发心绞痛的相关因素。
[Abstract]:Research background and purpose: metal matrix protease is an endogenous enzyme family which plays an important regulatory role in the degradation of extracellular matrix. Metal matrix protease 2 (matrix metalloproteinases, MMP2) is one of its family, also known as gelase A, and is involved in atherosclerotic plaques in the pathological state. The formation of block, plaque instability, coronary artery restenosis, hypertension, ventricular remodeling, heart failure and other processes. And it has been found that the gene polymorphism of MMP2-1306C/T affects the expression of MMP2 level through the regulation of transcriptional levels and thus causes increased risk of coronary heart disease and acute coronary syndrome (acute coronary syndrome, ACS). The study mainly through the detection of the MMP2-1306C/T gene loci of ACS patients, and explore the polymorphism of this site on the number of coronary vascular stenosis and its adverse prognosis in patients with ACS. Research objects and methods: collected at the First Affiliated Hospital of Dalian Medical University, the heart emergency and coronary heart disease one family in 2013 3 302 hospitalized patients diagnosed with ACS during the period from month to November were genotyping. The clinical data of the patients were collected in detail: test results, cardiac color Doppler (left ventricular diameter and ejection fraction), coronary angiography results, and the patients were followed up for at least one year, and the main end point of follow-up was the joint endpoint event. Death, angina, myocardial infarction, heart failure, arrhythmia, secondary end point was death during the follow-up period, recurrent angina, re infarction, heart failure, arrhythmia. 4 cases of failure and 60 patients in the process of gene detection were removed, and 238 cases were finally selected. Analysis and assessment of the effect of MMP2-1306C/T gene polymorphism on its prognosis: 1. genotype distribution: among 238 patients, 196 cases in group CC were 82.4%, 40 in group CT were 16.8%, 2 in group TT were 0.8%, and C alleles were 90.8%, and the frequency of T alleles was 9.2%.2. coronary stenosis branch. The ratio of single, double and multiple vascular stenosis showed a gradual decrease in the two groups in group CC and group CT/TT, but in the two groups, single branch 57.8%vs 56.2%, double branch 30.5%vs 31.3%, and three 11.7%vs 12.5%, the difference was not statistically significant in.3. clinical adverse prognosis: the patients were followed up for 23.2 + 1.5 months, close to half of the patients. The proportion of patients with angina pectoris had the highest proportion, 44.9% in group CC and 23.8% in group CT/TT, followed by heart failure, death, re infarction, and arrhythmia, the rate of recurrent angina was significantly increased in the lower.CC group compared with the CT/TT group, and P was 0.006, with a significant difference. The joint endpoint incident occurred. There was no significant difference in the incidence of single events such as birth rate and death, re infarction, arrhythmia, and heart failure. Among the 4 patients with CC genotype, 3 of the patients with re myocardial infarction were performed PCI, and none of the CT/TT genotype patients with PCI were compared with.4. for re myocardial infarction. The use of aspirin and statins was higher than 80% in the two groups. The use rate of beta blockers in group CC was 72.96%, and 85.71% in group CT/TT was higher than that in group CC. The use rate of clopidogrel and ACEI/ARB was slightly lower. However, there was no statistically significant difference between the two groups 5.. Age, sex, myocardial infarction, smoking, alcohol, hypertension, diabetes, blood lipid levels, fasting blood glucose, interventional therapy, taking aspirin, clopidogrel, ACEI/ARB, beta blocker, statins, and continuing to take these drugs as independent variables, two classified Logistic regression analysis, the results showed glycerin. The content of three fat, the content of high density lipoprotein, the level of fasting blood glucose, AMI and MMP2-1306CC were related to the angina pectoris. Conclusion: the gene phenotype of MMP2-1306C/T in 1.ACS patients is mostly CC, the frequency of CC genotypes and C alleles is significantly higher than that of CT/TT genotypes and T alleles, which is consistent with the previous studies at home and abroad. The frequency of recurrent angina in the 2-1306CC genotype was increased. The CC genotype was a risk factor for recurrent angina in ACS patients, indicating that the CC genotype may increase the instability of AS plaque, and the probability of reperfusion after CC genotype PCI may also increase. However, the effect of this genotype on ventricular remodeling is not found to be clear. There was no significant difference in the number of coronary artery stenosis in ACS patients with different MMP2-1306C/T gene phenotypes associated with.3.,.4.MMP2-1306CC, high level of glycerol three, low level of high-density lipoprotein and myocardial infarction as a risk factor for recurrent angina in ACS patients. Fasting blood glucose level was also a related factor for recurrent angina pectoris.

【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R541.4

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