江西省80例汉族人MMP-1基因多态性与COPD易感性的关系

目的 探讨中国南方汉族人群基质金属蛋白酶-1（MMP-1）基因多态性在慢性阻塞性肺疾病（COPD） 发病中的作用.方法 选择江西省80例吸烟COPD患者（观察组）及90例吸烟非COPD者（对照组）,应用PCR-限制性片段长度多态性法（PCR-RELP）检测两组MMP-1基因型.结果 观察组MMP-1基因突变型（2G/2G）、杂合型（2G/1G）、野生型（1G/1G）频率分布分别为65.0%（52/80）、27.5%（22/80）和7.5%（6/80）,对照组分别为54.4%（49/90）、28.9%（26/90）和16.7%（15/90）.观察组野生型MMP-1基因频率显著低于对照组（P〈0.05）.结论 中国南方汉族人群MMP-1基因多态性与COPD发病有关,野生型（G/G）MMP-1基因对COPD发病可能有预防作用.     

Ⅰ型基质金属蛋白酶基因C7936T多态与中国人脑卒中的关系

目的探讨Ⅰ型基质金属蛋白酶(Matrix Metalloproteinase-1,MMP-1)基因3'非翻译区C7936T多态性位点与中国人脑卒中的关系.方法采用限制性片段长度多态性分析技术,检测脑卒中组1636例和非脑卒中对照组1421例MMP-1基因C7936T多态的分布.结果脑卒中组和对照组MMP-1基因C7936T多态性基因型频数分布符合Hardy-Weinberg平衡.血栓性脑梗塞组具有TT基因型个体的频数(62.0%)高于对照组(55.7%),差异有统计学意义(P＜0.05);T等位基因频率分布也高于对照组(P＜0.05).腔梗组和脑出血组分别与对照组间基因频率分布差异无明显统计学意义.多元Logistic回归分析显示MMP-1基因C7936T多态性对血栓性脑梗塞的OR值为1.31(b=0.268,P=0.01,OR=1.31,95%CI1.065 1.605).结论 MMP-1基因C7936T多态可能是影响中国人群动脉粥样硬化性血栓性脑梗塞的遗传因素之一.     

白藜芦醇抑制可溶性CD40配体作用下巨噬细胞基质金属蛋白酶-9的表达

目的 探讨白藜芦醇抑制可溶性CD40配体(sCD40L)作用下对巨噬细胞基质金属蛋白酶-9(MMP-9)表达的影响.方法 佛波酯诱导人单核细胞株(THP-1)细胞分化为巨噬细胞.依次给予白藜芦醇和可溶性sCD40L孵育细胞,利用半定量反转录-聚合酶链反应(RT-PCR)、蛋白免疫印迹法、明胶酶谱法检测巨噬细胞内MMP-9和组织基质金属蛋白酶抑制因子-1(TIMP-1)基因的转录、蛋白表达和酶活性.结果 给予sCD40L刺激后巨噬细胞内MMP-9基因转录增多(1.53±0.04与0.75±0.01,P<0.05),蛋白分泌明显增加(244 930.8±31 268.6与192 976.8±20 223.1,P<0.05);白藜芦醇可抑制巨噬细胞MMP-9基因转录及蛋白分泌(P<0.01),降低MMP-9酶活性(P<0.05),升高巨噬细胞TIMP-1基因转录和蛋白分泌(P<0.05).结论 白藜芦醇可以抑制CD40途径活化的巨噬细胞内MMP-9的表达,调节MMP-9的活性,这可能是其抗动脉粥样硬化、稳定粥样斑块的作用机制之一.     

云南汉族人基质金属蛋白酶-1基因多态性与冠心病的相关性

目的研究基质金属蛋白酶-1（matrix metalloproteinase-1,MMP-1）基因多态性与冠心病发病的关系。方法用聚合酶链反应-限制性片段长度分析法分析经冠脉造影确诊的98例冠心病患者MMP-1启动区域-1607位点基因型,与同期102例非冠心病患者为对照组,比较两组之间MMP-1基因多态性频率分布的差异,并结合造影情况,探讨MMP-1基因多态性与冠脉狭窄程度的关系。结果冠心病患者MMP-1基因2G/2G型（0.41）明显低于正常对照者（0.56）,差异有显著性（P<0.05）。2G等位基因频率在冠心病组和对照组分别为0.61、0.72（P<0.05）;MMP-1基因1607-G/2G位点多态性分布与冠脉狭窄程度差异无统计学意义。结论MMP-1基因突变型（2G/2G）可能与冠心病遗传易感性有关。MMP-I基因-1607位点多态性与冠心病狭窄程度无关。     

预测急性冠状动脉综合征危险因素的候选基因多态性

目的:探讨中国汉族急性冠状动脉综合征(ACS)患者的易感性基因。方法:采用聚合酶链式反应/限制性片段长度多态性分析中国汉族108例患者(ACS组)和90例健康者(对照组)的4个候选基因,7个多态性。结果:ACS组基质金属蛋白酶-2(MMP-2)(-1306C/T)C等位基因频率与对照组比较差异有统计学意义(P<0.05),2组间3种基因型(CC、CT和TT)分布差异有统计学意义(P<0.05),而ACS组MMP-2(-1575G/A,-790G/T和-735C/T)、基质素-1(5A6A)、G蛋白β3亚单位(825C/T)和连接蛋白37(CX37)基因多态性(1019C/T)基因型分布和等位基因频率与对照组比较差异无统计学意义(P>0.05)。结论:MMP-2基因(-1306C/T)多态性可能与中国汉族人群ACS有关,MMP-2基因-1306C等位基因可能是ACS遗传易感性的基因标志之一。     

MMP-9基因多态性与IgA肾病病理改变的关系

目的 探讨基质金属蛋白酶-9(MMP-9) C-1562T基因多态性与IgA肾病病理改变间的关系.方法 应用聚合酶链反应-限制性片段长度多态性分析技术检测88例IgA肾病患者的MMP-9 C-1562T多态性,进一步研究其与IgA肾病病理分级间的相关关系.结果 IgA肾病患者MMP-9 C-1562T基因型分布频率为:CC基因型65例(73.9%),CT基因型23例(26.1%),TT基因型缺如.其基因型与IgA肾病病理分级比较,差异无显著性(P＞0.05).结论 MMP-9 C-1562T基因多态性可能不影响IgA肾病的病理改变和预后.     

基质金属蛋白酶-9与易损斑块

近年来许多的研究表明基质金属蛋白酶（MMP）尤其基质金属蛋白酶-9（MMP-9）在动脉粥样硬化的发生、发展和斑块稳定性中起重要作用，可以作为易损斑块的标志；同时MMP-9基因的C-1562T、R279Q和C＋6T核苷酸多态性可能与冠状动脉疾病和斑块稳定性相关，其中携带C-1562T和279R等位基因的动脉粥样硬化斑块患者具有较高的斑块破裂风险性。     

基质金属蛋白酶9基因多态性与慢性阻塞性肺疾病易感性的关系研究

基质金属蛋白酶（MMPs）基因是颇受关注的慢性阻塞性疾病（COPD）候选基因，MMP-9即是其中之一。有学者发现MMP-9启动子区域的多态性（-1562C/T）会影响酶的转录活性。探索酶基因表达产物活性的影响因素亦可能有助于阐明COPD的发病机制，为此我们应用限制性片段长度多态性（RFLP）方法，对江西籍汉族人COPD患者及健康对照者的MMP-9的启动子-1562位点基因型进行检测分析，报道如下。     

MMP-7基因-181A／G多态性与COPD易感性的相关性研究

目的探讨基质金属蛋白酶7（MMP-7）基因-18lA／G多态性与慢性阻塞性肺疾病（COPD）遗传易感性的关系。方法采用PCR-RELP方法检测100例COPD患者（COPD组）和年龄性别相匹配的100例健康对照者（健康组）MMP-7基因-181A／G多态性等位基因及基因型频率分布情况。结果两组MMP-7基因-181A／G不同位点多态性基因型频率分布均符合遗传性Hardy-Weinberg平街（P均〉0．05）。多态性检测结果显示,COPD组AA、AG和GG基因型频率分别为17％、48％和35％,健康组分别为18％,70％和12％,两组不同基因型频率分布有统计学意义（P=0．05）;COPD组G等位基因频率显著健康组（P=0．006）。结论MMP-7基因-180A／G多态性可能与COPD遗传易感性增加有关,G等位基因可能是COPD的易感基因。     

河北地区人群基质金属蛋白酶-2基因多态性与冠心病的相关性

目的 研究基质金属蛋白酶-2( MMP-2)基因启动子多态性与河北地区人群冠心病发病之间的关系.方法 采用聚合酶链式反应(PCR)扩增MMP-2启动子区包括-1306位点在内的基因序列,经测序后比较其基因型与冠心病发病风险和冠状动脉病变程度之间的关系.结果 冠心病组与对照组之间MMP-2基因型(- 1306 C/T)差异无统计学意义,其基因多态性在冠心病患者冠状动脉病变程度之间亦无统计学差异.结论 MMP-2单核苷酸多态性-1306(C/T)与冠心病的遗传易感性无关,与其冠状动脉病变程度无关.     

Functional polymorphisms in matrix metalloproteinase-1 and monocyte chemoattractant protein-1 and rheumatoid arthritis

The aim of this study is to investigate whether the functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1) and in the regulatory region of the monocyte chemoattractant protein-1 (MCP-1) gene are associated with susceptibility to rheumatoid arthritis (RA) and its clinical features. The MMP-1 1G/2G polymorphism and the MCP-1 promoter A/G polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism in 117 RA patients and 97 healthy controls. The genotype distribution of the MMP-1 promoter did not differ between RA patients and control subjects. However, in the 2G/2G genotype, ESR and Plat were higher than the 1G/1G genotype. The genotype distribution of the MCP-1 promoter did not differ between the RA and control groups. Clinically there was no significant difference among RA patients according to the MCP-1 promoter genotypes. Our data show that the functional promoter polymorphism in the MMP-1 promoter may not play an important role in the susceptibility of RA, but the polymorphism may be related to clinical phenotypes.     

Matrix Metalloproteinase (MMP)-3 Polymorphism in Patients with HBV Related Chronic Liver Disease

A common and important problem in patients with chronic hepatitis B is the progression of liver fibrosis. Matrix metalloproteinases (MMPs) play an important role in the progression of liver fibrosis. Our aim of this study was to examine the association of MMP-3 polymorphism with liver cirrhosis in Korean patients with chronic hepatitis B. Genomic DNA was extracted from 127 patients with chronic hepatitis B (CHB), 92 patients with hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC), and 146 healthy subjects. MMP-3 polymorphism was determined by polymerase-chain reaction-based assays, and the association with the progression of liver cirrhosis was investigated. With regard to MMP-3 polymorphism, there was no statistical difference in genotype distributions among the three groups. However, the peripheral platelet count of the 5A carriers was significantly lower than that of the 6A homozygotes in the HBV-LV group (85.0 ± 36.9 vs. 109.8 ± 47.0 × 10⁹/l; P = 0.02). With MMP-3 promoter polymorphism (rs3025058), a lower peripheral blood platelet count, which was related to advanced liver cirrhosis, was observed in 5A carriers. Therefore, more studies of MMP-3 gene polymorphism with larger populations should be conducted to further understand its role in the progression of liver cirrhosis.     

Analysis of MMP-7 and TIMP-2 gene polymorphisms in coronary artery disease and myocardial infarction: A Turkish case-control study

Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) have a significant role in tissue remodeling related to cardiac function. In earlier studies, MMP-7 A-181G (rs11568818), C-153T (rs11568819), C-115T (rs17886546), and TIMP-2 G-418C (rs8179090) polymorphisms have been studied in various diseases. However, association between coronary artery disease (CAD) and these polymorphisms has been poorly studied. The goal of this study is to investigate the association of CAD and myocardial infarction (MI) with MMP-7 or TIMP-2 polymorphisms. This study included 122 CAD patients and 132 control individuals. DNA was extracted from whole blood. Polymerase chain reaction-restriction fragment length polymorphism and automated direct sequencing method were used for genotyping of these polymorphisms. No significant differences were found between MMP-7 A-181G, C-115T, and TIMP-2 G-418C polymorphism and CAD or MI in a Turkish population. Despite the fact that the genotypes of MMP-7 C-153T polymorphism had no significant differences among MI and control groups, allele frequencies of C-153T polymorphism were significantly different between the two groups. Our study is the first report to clarify the appreciable relationship between MMP-7 C-153T polymorphism and MI development in CAD patients. However, these findings also need to be confirmed in other populations so we can improve our knowledge about the genetic factors affecting the development of CAD.     

Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid arthritis: a prospective longitudinal study

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by chronic synovitis leading to permanent damage of the joints. Collagenase-1 (MMP-1) is a matrix metalloproteinase involved in articular cartilage degradation. We investigated the association between a biallelic polymorphism in the MMP-1 gene promoter and the susceptibility to, and severity of, RA. We also investigated the association between HLA-DRB1 gene polymorphism and severity of RA. METHODS: One hundred and three patients with early RA were included in this prospective longitudinal study. A radiographic damage score was used to quantify disease severity at baseline and after 4 years of followup. MMP-1 polymorphism genotyping was analyzed using a fluorescent-based polymerase chain reaction (PCR). HLA-DRB1 genotypes were determined by PCR sequence-specific oligonucleotide probes. One hundred and thirty-three healthy individuals were used as controls. RESULTS: MMP-1 allele and genotype frequencies did not differ between RA patients and controls. The radiographic damage or its progression over the 4 years of followup did not differ across MMP-1 genotypes. The radiographic damage score and its progression over the 4 years of followup differed across HLA-DRB1 genotypes. The HLA-DRB I shared epitope +/+ genotype was associated with the highest radiographic damage score and the highest progression, while the shared epitope -/- genotype was associated with the lowest. CONCLUSION: Our results do not support the hypothesis of an association between this particular polymorphism in the MMP-1 gene promoter and susceptibility to, or severity of, RA. This study confirms the previous reports of an association between the HLA-DRB1 gene polymorphism and severity of RA.     

Matrix metalloproteinase-1 polymorphism in Taiwanese patients with endobronchial tuberculosis

Endobronchial tuberculosis (TB) often leads to some degree of tracheobronchial stenosis. Because matrix metalloproteinases (MMPs) play an essential role in tissue remodeling in the airways, we investigated the role of MMP-1 polymorphism in patients with endobronchial TB. One hundred and one cases of pulmonary TB in Taiwanese patients were genotyped for the 1G/2G polymorphism of MMP-1 promoter (-1607 bp). Bronchoscopic examination was performed to determine the presence of endobronchial involvement. Levels of MMP-1 in peripheral blood monocytes and in bronchial biopsies were also determined. 1G genotypes of MMP-1 polymorphism, containing at least one 1G allele, were associated with the presence of endobronchial TB. Using multivariate analysis, 1G genotypes and female gender were independent predictors of the development of endobronchial TB. Endobronchial TB patients with 1G genotypes had a 9.86-fold greater risk of developing tracheobronchial stenosis. IL-1beta increased levels of MMP-1 in peripheral blood monocytes of TB patients with 1G genotypes. MMP-1 activity was also present in the endobronchial TB granuloma from patients with 1G/1G genotype. 1G genotypes of MMP-1 polymorphism were associated with a greater risk of developing tracheobronchial stenosis through up-regulation of MMP-1 activity.