心肌梗死患者基质金属蛋白酶9基因C1562T多态性

目的研究基质金属蛋白酶9基因C1562T多态性与中国汉族人群心肌梗死易感性的关系。方法以78例经冠状动脉造影确诊的心肌梗死患者为研究对象，以同期冠状动脉造影阴性、排除冠心病诊断的81例患者为时照组，取外周血标本提取DNA，用聚合酶链反应方法扩增目的基因，用限制性内切酶酶切聚合酶链反应产物用于基因分型。比较两组间基质金属蛋白酶9基因多态性频率分布的差异。结果本研究中未发现基质金属蛋白酶9的TT基因型突变。心肌梗死患者基质金属蛋白酶9基因CT基因型频率（26．9％）高于对照组（9．9％），两组差别有统计学意义（x^2=7．743，P=0．005），心肌梗死组1562T等位基因频率（13．5％）高于对照组（4．9％），两组差别也有统计学意义（x^2=6．966，P=0．008）。结论基质金属蛋白酶9基因C1562T多态性与中国汉族人群心肌梗死有关，1562T等位基因可能是心肌梗死遗传易感性的基因标记之一。     

急性冠状动脉综合征患者基质金属蛋白酶9基因多态性

目的 探讨基质金属蛋白酶9基因C1562T多态性与中国南方汉族人群冠心病的关系.方法 对经冠状动脉造影证实的急性冠状动脉综合征患者150例(急性冠状动脉综合征组)、稳定型心绞痛患者110例(稳定型心绞痛组)和同期冠状动脉造影阴性、排除冠心病诊断的患者70例(对照组)进行研究,采用酶联免疫吸附试验测定血浆基质金属蛋白酶9水平,采用聚合酶链反应-限制片长多态性技术分析基质金属蛋白酶9基因中C1562T基因多态性,比较各组的基因型和等位基因频率.结果 急性冠状动脉综合征组血浆基质金属蛋白酶9水平明显高于稳定型心绞痛组(P＜0.05)和对照组(P＜0.01),而稳定型心绞痛组与对照组比较,差异无统计学意义(P＞0.05).急性冠状动脉综合征组基质金属蛋白酶9基因CT、CT TT基因型频率以及T等位基因频率均高于对照组和稳定型心绞痛组(P＜0.05或0.01),稳定型心绞痛组与对照组各基因型和等位基因频率分布差异无统计学意义(P＞0.05).C1562T位点CT/TT基因型患者血浆基质金属蛋白酶9水平显著高于CC基因型患者(P＜0.01).结论 基质金属蛋白酶9基因C1562T多态性可能与中国南方汉族人群急性冠状动脉综合征有关,1562T等位基因是动脉粥样硬化斑块不稳定性的易感基因.     

基质金属蛋白酶-9基因多态性与原发性高血压发病的相关性

目的基质金属蛋白酶（MMP）-9是一种基质降解酶,可能参与了血管的重构。本研究旨在探讨MMP-9基因C-1562T多态性与高血压及性别的相关性。方法采用聚合酶链反应结合限制性内切酶片段长度多态性分析,分别检测北京宣武医院门诊807例原发性高血压患者和同一地区509例正常对照的MMP-9基因C-1562T多态性。电泳判断基因型并测序。结果高血压组TT＋CT基因型频率和T等位基因频率显著高于正常对照组（28．7％vs22．6％,15．4%vs12．7％;P〈0．05）。女性中高血压组的TT＋CT基因型频率和T等位基因频率显著高于正常对照组（31．0％vs22．0％,16．6％vs12．1％;P〈0．05）,T等位基因对高血压的OR值为1．442（CI：1．057～1．968）。男性中两组基因型无显著差别。老年女性高血压组的TT＋CT基因型频率和T等位基因频率显著高于老年男性高血压组、老年女性正常对照组和非老年女性高血压组。结论MMP9基因-1562T等位基因可能是老年女性原发性高血压的危险因素。     

基质金属蛋白酶-9基因C1562T多态性与高血压颈动脉粥样硬化关系

目的:研究基质金属蛋白酶-9(MMP-9)基因C1562T多态性与高血压颈动脉粥样硬化的相关性。方法:原发性高血压患者120例,测定受试者双侧颈动脉内-中膜厚度(IMT),IMT≥1.3mm认为存在粥样硬化斑块。依颈动脉有无粥样硬化分为颈动脉粥样硬化组、颈动脉正常组。用聚合酶链反应-限制性片段长度多态性分析法分析2组患者的MMP-9基因C1562T的多态性。结果:颈动脉粥样硬化组与颈动脉正常组CT TT基因型频率分别为28.8%、13.2%,差异有统计学意义(χ2=4.488,P=0.034),T等位基因与颈动脉粥样硬化发病密切相关(OR=2.092,95%CI:0.991~4.419,P=0.047)。结论:MMP-9T等位基因与高血压颈动脉粥样硬化密切相关,可能是其遗传标志。     

Association of (-1,607) 1G/2G polymorphism of matrix metalloproteinase-1 gene with knee osteoarthritis in the Turkish population (knee osteoarthritis and MMPs gene polymorphisms)

The aim of this study was to investigate whether functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were associated with susceptibility to knee osteoarthritis in the Turkish population. The MMP-1 −1,607 1G/2G (rs1799750), MMP-2 −1,306 C/T (rs243865), and MMP-9 −1,562 C/T (rs3918242) polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assay in 157 patients diagnosed with knee osteoarthritis based on the criteria of American College of Rheumatology and in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients and controls. There were significant differences between the groups regarding the genotype distribution of MMP-1 polymorphism (P  = 0.001). The frequencies of 1G/1G and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in the controls (P = 0.002, and P =  0.006, respectively). In addition, 1G allele frequency of MMP-1 gene was higher in the patients than in the control group (P = 0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9 gene polymorphisms did not differ between the osteoarthritis and the control groups (P > 0.05). These findings suggest that the −1,607 1G/2G polymorphism in the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the Turkish population.     

Genetic polymorphism in matrix metalloproteinase-9 and transforming growth factor-β1 and susceptibility to combined pulmonary fibrosis and emphysema in a Chinese population

In this study, we aimed to explore the association of genetic polymorphism in matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) and the susceptibility to combined pulmonary fibrosis and emphysema (CPFE). We examined the polymorphisms of the MMP-9 C-1562T and TGF-β1 T869C in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The frequencies of polymorphic genotypes in MMP-9 were 78.95% CC and 21.05% CT in CPFE group, 76.0% CC and 24.0% CT in emphysema group, and 100.0% CC in IPF group. There were highly statistically significant increased frequencies of the CT genotype and T allele in CPFE and emphysema groups compared with IPF group (p < 0.05). The frequencies of polymorphic genotypes in TGF-β1 were 2.63% CC, 28.95% CT, 68.42% TT in CPFE group, 4.00% CC, 16.00% CT, 80.00% TT in emphysema group, and 5.88% CC, 41.18% CT, 52.94% TT in IPF group. Significant increases in the TT genotype and T allele frequencies were observed in emphysema group compared with IPF group (p < 0.05). Our study has showed that T allele in MMP-9 (C-1562T) and T allele in TGF-β1 (T869C) are risk factors of pulmonary emphysema. The T allele in MMP-9 (C-1562T) possibly predisposes patients with pulmonary fibrosis to develop emphysema.     

基质金属蛋白酶9及其启动子C-1562T基因多态性与冠心病的相关性研究

目的探讨基质金属蛋白酶9（MMP-9）及其启动子C-1562T基因多态性在冠心病发病中的作用及其临床意义。方法入选163例患者,冠心病组103例,其中急性冠脉综合征（ACS）组71例,稳定型心绞痛（SAP）组32例;对照组60例。采用限制性内切酶片段长度多态性（PCR—RFLP）法鉴定MMP-9启动子C-1562T基因型,所有患者均行冠脉造影检查明确冠状动脉病变情况。结果①冠心病组MMP-9启动子-1562C／T基因型频率较对照组增高,-1562T型等位基因频率增高,差异有统计学意义。②冠心病患者MMP-9浓度较对照组明显升高,差异有统计学意义。③有T型等位基因患者MMP-9浓度较无T型等位基因患者升高,差异有统计学意义。④冠心病与其危险因素logistic回归分析提示,吸烟、高血压、高脂血症、肥胖、MMP-9启动子-1562T型等位基因为冠心病的危险因素。结论MMP-9启动子C-1562T基因多态性与冠心病的发病可能相关,T型等位基因可能是冠心病患者遗传易感性基因标志之一。MMP-9启动子C-1562T型等位基因可能引起MMP-9表达增高。     

Matrix metalloproteinase gene polymorphisms in patients with rheumatoid arthritis

Several genetic factors seem to be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to analyze whether functional polymorphisms in the promoter region of the MMP-1, -3 and -9 genes were associated with RA. The study population comprises 110 RA patients and 100 healthy controls. The –1607 1G/2G MMP-1, –1171 5A/6A MMP-3, and –1562 C/T MMP-9 polymorphisms were analyzed. The frequency of the 5A allele of MMP-3 gene was significantly higher in the controls when compared with the RA patients (0.45 vs. 0.32, P < 0.01). No significant differences were observed in the allele frequencies for the MMP-1 and -9 polymorphisms between RA patients and controls. Individuals carrying MMP-3 5A allele have significant higher frequency of extra-articular manifestations and rheumatoid nodules than individuals homozygous for 6A allele (P < 0.05). The results presented in this study provide evidence of an association between the MMP-3 gene polymorphism and RA.     

Effect of matrix metalloproteinase-9 -1562C/T gene polymorphism on manifestations of pulmonary tuberculosis

Increased levels of matrix metalloproteinase-9 (MMP-9) in patients with tuberculous meningitis, tuberculous pleuritis, and advanced pulmonary tuberculosis (TB) suggest a pivotal role for MMP-9 in the development of pulmonary TB and its clinical manifestations. The present study was performed to evaluate the role of the -1562C/T single nucleotide polymorphism (SNP) in the promoter region of the human MMP-9 gene in development of pulmonary TB and its radiographic characteristics. A case-control study was performed with a study population of 205 patients with pulmonary TB and 223 healthy controls. Differences were explored in the allele and genotype distributions of the -1562C/T polymorphism between patients with pulmonary TB and healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavities. The -1562C/C genotype was more common in patients with multi-lobe involvement than in those with single-lobe involvement (81.8 vs. 67.6%, P=0.03). However, there were no significant differences in the distribution between patients with pulmonary TB and healthy controls (P=0.40) or between patients with and without cavities (P=0.18). These results suggest that the -1562C/C genotype is associated with the intrapulmonary spread of TB rather than its development.     

基质金属蛋白酶-9及血小板膜糖蛋白Ⅵ基因多态性与急性冠状动脉综合征的相关性研究

目的探讨金属蛋白酶（MMP-9）血浆水平、基因多态性与血小板膜糖蛋白Ⅵ（GPⅥ）基因多态性在急性冠状动脉综合征（ACS）发病中的作用及其相关性。方法对179例经冠状动脉造影及临床表现证实为ACS的患者与164例经冠状动脉造影证实无冠状动脉病变的对照者进行研究,采用ELISA法测定血浆MMP-9水平;Clauss法测定纤维蛋白原（Fib）水平;采用多聚酶链反应-限制性内切酶片断长度多态性（PCR-RFLP）分析MMP-9基因中C-1562T、G5564A和GPⅥ T13254C、Fib Bβ链-148C／T基因多态性。结果ACS组血浆MMP-9和Fib水平明显高于对照组,P 〈 0．001;急性心肌梗死组的血浆Fib水平高于不稳定性心绞痛组,P 〈 0．05。ACS组与对照组比较．MMP-9／C-1562T、MMP-9／G5564A和GPⅥ T13254C、Fib Bβ链-148C／T基因型与等位基因频率分布差异无统计学意义。当Fib Bβ链出现T等位基因时,血浆Fib水平明显升高,P 〈 0．05。显示MMP-9及Fib与ACS发病呈明显正相关（ r = 0．289,P 〈 0．01）。结论MMP-9及Fib是ACS发病的独立危险因素,Fib Bβ链T等位基因与血浆Fib水平升高有关,MMP-9 C-1562T、G5564A和GPⅥ T13254C、FibBβ链-148C／T等位基因频率分布在ACS组对照组之间差异无统计学意义。     

Modulating effects of matrix metalloproteinase-3 and -9 polymorphisms on aortic stiffness and aortic root dilation in patients after tetralogy of Fallot repair

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix proteins, which are important determinants of arterial stiffness. This study aimed to test the hypothesis that MMP-3 and MMP-9 polymorphisms may modulate aortic stiffness and magnitude of aortic root dilation in patients after surgical repair of tetralogy of Fallot (TOF). We analyzed the MMP-3 promoter and MMP-9 −1562 C > T polymorphism in 79 TOF patients aged 19.9 ± 9.5 years and determined their associations with aortic stiffness and sinotubular dimension. Genotypic and allelic frequencies of MMP-3 for the 6A6A genotype and MMP-9 for the T allele did not differ between patients and published control data (all p > 0.05). For the MMP-3 locus, patients with a 6A6A genotype and those with a 6A6A/5A6A genotype had similar aortic stiffness (p = 0.60), heart-femoral pulse wave velocity (p = 0.63), and z score of sinotubular junction (p = 0.81). For the MMP-9 locus, the −1562T allele carriers had significantly lower aortic stiffness (p = 0.005), slower heart-femoral pulse wave velocity (p = 0.03), and smaller z score of sinotubular junction (p = 0.047). Multivariate linear regression identified MMP-9 polymorphism (β = −0.31, p = 0.005) as a significant correlate of aortic stiffness after adjustments for age at study, age at operation, sex, body mass index, systolic and diastolic blood pressures, and MMP-3 polymorphism. In conclusion, MMP-9 but not MMP-3 polymorphism exerts a modulating influence on aortic stiffness and aortic root dilation in patients after TOF repair.     

高血压合并主动脉夹层基质金属蛋白酶9基因-1562C/T多态性

目的探讨高血压病合并主动脉夹层患者基质金属蛋白酶9（MMP-9）基因一1562C／T基因多态性与临床表现的关系。方法对高血压病合并主动脉夹层患者及高血压病患者用酚一氯仿法提取外周血基因组DNA,PCR-限制性片段长度多态性法确定MMP-9基因一1562C／T基因型。结果（1）高血压病合并主动脉夹层患者中,MMP-9基因一1562T等位基因频率（17．6％）显著高于高血压病患者（11．2％,P〈0．05）,两组之间3种基因型（-1562CC、-1562CT、-1562Tr）分布差异无统计学意义（P〉0．05）。（2）与-1562CC基因型相比,基因型为-1562CT／TT的主动脉夹层患者累及升主动脉更多见（OR=2．063,95％CI=0．998～4．264,P=0．049）。结论MMP-9基因-1562T多态性与中国汉族人群高血压病并主动脉夹层的发病可能相关,T等位基因可能是高血压病并发主动脉夹层的遗传易感因素之一;携带MMP-9基因-1562T等位基因的高血压病合并主动脉夹层患者更多累及升主动脉,影响预后。     

Matrix metalloproteinase-9-1562C〉T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer

AIM: To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population. METHODS: Genotyping of MMP-9 -1562C>T and 279R>Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The distribution of MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph node metastasis of CRC was increased in patients with the -1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP-9 279RR RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102; 95% CI = 0.013-0.812; P = 0.012). CONCLUSION: Our results indicated that the MMP-9-1562C>T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.     

基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究

目的 探讨基质金属蛋白酶9(MMP-9)基因C-1562T多态性与2型糖尿痫血管病变的关系．方法 运用PCR-RFLP检测110名健康对照者和450例2型糖尿病(DM)患者(其中单纯2型DM者100例、大血管病变者120例、糖尿病肾病(DN)患者130例、糖尿病视网膜病变患者100例)的MMP-9基因型，比较各组的基因型和等位基因频率。结果 (1)所有糖尿病视网膜病变患者的基因型均为CC型。(2)与对照组和单纯2型DM组相比，大血管病变组的T基因型和T等位基因频率显著升高，而DN组的TT基因型和T等位基因频率明显下降。(3)Logistic回归分析显示MMP-9 T等位基因、血清MMP-9、总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)是大血管病变发生的危险因素；尿白蛋白排泄率、脂蛋白(a)、HbA1C是DN发生的危险因素。结论 MMP-9基因C-1562T多态性与2型DM血管病变的发生有关，T等位基因是大血管病变的易感基因，是DN的保护基因。     

SDF-1alpha G801A polymorphism in Southern Iranian patients with colorectal and gastric cancers

Background

A single nucleotide polymorphism (SNP) in the stromal cell-derived factor-1 (SDF-1) gene at position 801 (G>A) is associated with susceptibility to certain tumors. This study aimed to investigate an association between this SNP and colorectal and gastric cancers in an Iranian population.

Method

Genotype and allele frequencies of SDF-1 801 G>A were assessed using polymerase chain reaction-restriction fragment length polymorphism in 109 patients with colorectal cancer, 124 with gastric cancer, and 262 normal control volunteers.

Results

No statistically significant difference was observed in the frequencies of genotypes and alleles between patients and controls (p?>?0.05).

Conclusion

SDF-1 gene polymorphism at position 801 (G>A) was not associated with colorectal and gastric cancers in Southern Iranian patients.     

Matrix metalloproteinase 9 (MMP-9) gene polymorphism and MMP-9 plasma levels in primary Sjogren's syndrome

OBJECTIVES: To determine whether plasma matrix metalloproteinase 9 (MMP-9) and MMP9 (-1562C-->T) polymorphism have an effect on the disease phenotype in primary Sjogren's syndrome (pSS). METHODS: Plasma MMP-9 concentrations and polymorphism of the MMP9 gene were analysed in 66 patients with pSS. These data were studied in relation to the clinical data of the patients. The genetic data of patients were compared with the data of 66 healthy subjects. RESULTS: Plasma MMP-9 was higher in patients with definite pSS than in patients with possible pSS. This association was principally caused by higher plasma MMP-9 in patients with a positive Schirmer test and keratoconjunctivitis sicca. pSS patients with purpura, SS-A autoantibodies and RF had significantly lower plasma MMP-9 than patients without these characteristics. The overall MMP9 (-1562C-->T) allele frequencies were similar in patients and control subjects. The frequency of the allele T was higher in patients without Raynaud's phenomenon than in the control group. CONCLUSIONS: MMP9 (-1562C-->T) could not be used for risk assessment in pSS. The presence of the rarer allele T may decrease the risk of Raynaud's phenomenon in pSS. High plasma MMP-9 is indicative of definite pSS but may paradoxically have a preventive effect on the eruption of purpura and on the development of autoantibody reaction in pSS.     

The C(-1562)T polymorphism in the promoter of the matrix metalloproteinase-9 (MMP-9) gene and coronary atherosclerosis

Atherosclerosis of coronary arteries is a main cause of ischaemic heart disease (IHD). Matrix metalloproteinases, a super-family of zink-dependent enzymes, which are involved in the pathogenesis of atherosclerosis by the activation of migration and proliferation of smooth muscle cells and by the induction of destabilization of atherosclerotic plaques. Some observations suggest that C(-1562)T polymorphism of matrix metalloproteinase-9 (MMP-9) promoter predisposes to multivessel IHD. Therefore, the aim of our study was to evaluate the association between C(-1562)T MMP-9 polymorphism and angiographically-documented coronary atheroclerosis in 110 patiens. Genomic DNA isolated from peripheral blood nuclear cells was amplified by PCR method with pair of primers flanking the polymorphic regions and subsequently MMP-9 genotypes were identified by amplicon digestion with Pac I restriction enzyme. The T(-1562) allel was idientified by gain of restriction site. There were 67 CC homozygotes and 43 carriers of T allele (41 CT + 2 TT). No differences has been found among patiens with various number of significantly stenotic (>50%) coronary arteries (group 0, 1, 2 and 3, respectlively) in genotype distribution, age, prevalance of arterial hypertension, and plasma concentrations of triglycerides, cholesterol and fibrinogen. However, in subjects younger < 50 years, the frequency of T(-1562) allele was significantly higher in IHD patients as compared with controls (group O). Results of our preliminary study suggest, that C(-1562)T MMP-9 transition is associated with premature IHD in Polish patients.     

基质金属蛋白酶-9基因单核苷酸多态性与冠状动脉血管狭窄的相关性

目的研究我国河北省汉族人群基质金属蛋白酶-9(MMP-9)基因单核苷酸多态性-1562C>T与冠心病患者冠状动脉狭窄程度的相关性。方法收集经冠状动脉造影证实的冠心病患者91例和101例正常对照者,采用聚合酶链反应后直接测序的方式检测个体的基因型;比较不同基因型与血管狭窄的关系,并分析基因型与狭窄程度的关系。结果血管狭窄病例组和对照组MMP-9 C1562T C/C,C/T,T/T基因型分布频率无差异;C等位基因频率无显著差异;病例组之间各基因型和等位基因频率无显著性差异。结论 C1562T多态可能与冠心病的发生无关。