LR99ES11, Department of Biochemistry, La Rabta Hospital, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia.
Faculty of Mathematics, Physics and Natural Sciences, University of Tunis El Manar, Tunis, Tunisia.
Mol Biol Rep. 2022 Oct;49(10):9171-9179. doi: 10.1007/s11033-022-07742-1. Epub 2022 Aug 12.
Matrix metalloproteinases (MMPs) are widely expressed in atherosclerosis lesions. The disequilibrium of MMPs driving to an overexpression or a lack of its level can be influenced by genetic variations. MMP-3 and MMP-9 may be affected by specific polymorphisms like - 1612 5 A/6A and the - 1562 C/T respectively. We aim in the present study to investigate prospectively the association between the - 1612 5 A/6A MMP-3 and - 1562 C/T MMP-9 polymorphisms and clinical outcomes in patients with coronary artery disease (CAD). This study is elaborated to reveal whether one of these polymorphisms is a probable predictor of cardiovascular complications in this CAD cohort.
A total of 168 patients with CAD were prospectively followed up over a period of 5 years. Genotypes for the MMP-3 (-1612 5 A/6A) and MMP-9 (-1562 C/T) polymorphisms were performed using PCR-RFLP. Their levels were measured by ELISA in Sandwich test during the follow-up period, 39 cardiovascular outcomes occurred with 21 repeat targets for revascularization, 3 patients with Myocardial infarction, 8 for heart failure, 5 for Stroke and 2 for cardiovascular mortality. The MMP-3 5 A/6A polymorphism was related to the disease on the contrary of the MMP-9 -1562 C/T. Patients carrying the 5 A allele had a higher level of MMP-3 level and those who carried the 6 A allele had lower level (p = 0.04). After applied multivariable Cox-hazard models we revealed that the 6 A allele is independently associated to the disease complication. Kaplan-Meier survival test revealed that individuals having the 6 A allele had a lower survival rate than those with the 5 A allele (p = 0.04).
Our study suggests the disruption of the MMP-3 level may be due to the existence of the polymorphism - 1612 residing in its promoter region. MMP-3 can be considered as a marker of diagnosis and prediction in cardiovascular events.
基质金属蛋白酶（MMPs）广泛存在于动脉粥样硬化病变中。MMPs 的失衡导致其表达过度或缺乏，这种失衡可能受到遗传变异的影响。MMP-3 和 MMP-9 可能受到特定的多态性的影响，如 -1612 5A/6A 和 -1562C/T。我们旨在本研究中前瞻性地研究基质金属蛋白酶-3（MMP-3）的 -1612 5A/6A 多态性和基质金属蛋白酶-9（MMP-9）的 -1562C/T 多态性与冠心病（CAD）患者临床结局之间的关系。本研究旨在揭示这些多态性之一是否是 CAD 患者心血管并发症的一个可能预测因子。
共前瞻性随访 168 例 CAD 患者 5 年。使用 PCR-RFLP 法检测 MMP-3（-1612 5A/6A）和 MMP-9（-1562C/T）多态性。在随访期间通过夹心试验 ELISA 法检测 MMP-3 水平。共发生 39 例心血管事件，其中 21 例进行了血运重建，3 例心肌梗死，8 例心力衰竭，5 例卒中和 2 例心血管死亡。MMP-3-16125A/6A 多态性与疾病相关，而 MMP-9-1562C/T 多态性与疾病无关。携带 5A 等位基因的患者 MMP-3 水平较高，携带 6A 等位基因的患者 MMP-3 水平较低（p=0.04）。应用多变量 Cox 风险模型后发现，6A 等位基因与疾病并发症独立相关。Kaplan-Meier 生存分析显示，携带 6A 等位基因的个体生存率低于携带 5A 等位基因的个体（p=0.04）。
我们的研究表明，MMP-3 水平的破坏可能是由于其启动子区域存在多态性 -1612。MMP-3 可作为心血管事件诊断和预测的标志物。
