Spurthi Kondapalli Mrudula, Galimudi Rajesh Kumar, Srilatha Gantala, Sahu Sanjib Kumar, Nallari Pratibha, Hanumanth Surekha Rani
Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh, India.
Genet Test Mol Biomarkers. 2012 Aug;16(8):850-4. doi: 10.1089/gtmb.2011.0299. Epub 2012 Jul 18.
Atherosclerosis, the underlying pathology of cardiovascular disease, is a common, multifactorial disorder with both genetic and environmental components as risk factors. Gelatinase B, also known as MMP-9, is one of the matrix metalloproteinases that is highly expressed in the disruption-prone regions of atherosclerotic plaques. It has been hypothesized that a genetic variation affecting the expression or activity of MMP-9 influences the susceptibility and progression of atherosclerosis. The present study aims to ascertain the polymorphic variants of the MMP-9 gene promoter and its serum levels, which contribute to interindividual differences in susceptibility to atherosclerosis. The study population consisted of 200 individuals who include 100 cases with angiographically recorded coronary artery disease (CAD) and 100 age- and sex-matched healthy controls. Serum levels of MMP-9 were determined in these subjects using an enzyme-linked immunosorbent assay, and polymorphic genotypes of MMP-9 were determined by the polymerase chain reaction-restriction fragment length polymorphism assay.
The MMP-9 levels among subjects with the TT genotype for controls (12.21±2.39) and CAD (22.86±2.45) were significantly higher than that of CC genotype (controls 10.37±1.42 and CAD 16.44±7.99), and the values were intermediate for the CT genotype (control 11.21±2.01 and CAD 18.80±3.17) and found to be significant at p<0.01. Genotypic analysis of -1562C/T polymorphism among patients and controls showed higher T allele frequencies in the patient group (0.36) than in the controls (0.29).
It has been observed that increased MMP-9 expression in T allele carriers may contribute to the severity of coronary atherosclerosis. These findings not only are relevant to the understanding of the pathogenesis of atherosclerosis but also may provide a novel target for future development of predictive, preventive, and therapeutic measures.
动脉粥样硬化是心血管疾病的潜在病理基础，是一种常见的多因素疾病，遗传和环境因素均为风险因素。明胶酶B，也称为基质金属蛋白酶-9（MMP-9），是在动脉粥样硬化斑块易破裂区域高度表达的基质金属蛋白酶之一。据推测，影响MMP-9表达或活性的基因变异会影响动脉粥样硬化的易感性和进展。本研究旨在确定MMP-9基因启动子的多态性变异及其血清水平，这些因素导致个体对动脉粥样硬化易感性的差异。研究人群包括200名个体，其中100例经血管造影记录为冠心病（CAD）患者，以及100名年龄和性别匹配的健康对照。采用酶联免疫吸附测定法测定这些受试者的血清MMP-9水平，并通过聚合酶链反应-限制性片段长度多态性分析确定MMP-9的多态基因型。
对照组（12.21±2.39）和CAD组（22.86±2.45）中TT基因型受试者的MMP-9水平显著高于CC基因型（对照组10.37±1.42，CAD组16.44±7.99），CT基因型的值处于中间水平（对照组11.21±2.01，CAD组18.80±3.17），p<0.01时差异具有统计学意义。患者和对照组中-1562C/T多态性的基因型分析显示，患者组的T等位基因频率（0.36）高于对照组（0.29）。
已观察到T等位基因携带者中MMP-9表达增加可能导致冠状动脉粥样硬化的严重程度。这些发现不仅有助于理解动脉粥样硬化的发病机制，还可能为未来预测、预防和治疗措施开发提供新靶点。
