Dataset Information

Impact of matrix metalloproteinase-8 gene variations on the risk of thoracic aortic dissection in a Chinese Han population.

ABSTRACT: The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease progression in TAD were investigated. The level of plasma and tissue MMP8 was measured by enzyme-linked immunosorbent assay and western blotting. The MMP8 C-799T polymorphism was significantly associated with susceptibility to disease progression in TAD patients (n = 152) than in controls (n = 147) (P = 0.004, OR = 0.62, 95 % CI 0.45-0.86). The TT homozygotes had a significantly higher risk of TAD compared to C allele carriers in a logistic regression model, after adjustment for the conventional risk factors for TAD. The plasma MMP8 concentration was significantly higher in TAD patients compared to control patients (P < 0.05). TT genotypes had increased MMP8 levels compared to CC and CT genotype carriers in both TAD and control subjects (P < 0.05). The C-799T polymorphism in the MMP8 promoter is part of the genetic variation underlying the susceptibility of individuals to the progression of TAD.

SUBMITTER: Wang XZ

PROVIDER: S-EPMC3824396 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Impact of matrix metalloproteinase-8 gene variations on the risk of thoracic aortic dissection in a Chinese Han population.

Wang Xiao-Zeng XZ Du Xiao-Mo XM Jing Quan-Min QM Li Xing-Xing XX Gu Ruo-Xi RX Wang Jiao J Han Ya-Ling YL

Molecular biology reports 20130925 10

The importance of matrix metalloproteinase 8 (MMP8) expression during the progression of thoracic aortic dissection (TAD) has been recently emphasized. Genetic variations that affect proteinase expression or activity might contribute to the pathogenesis of TAD. In this study, we investigated whether the MMP8 C-799T genotype is associated with TAD. The frequency distributions of the MMP8 C-799T polymorphism were determined by direct sequencing. Associations between the polymorphism and disease pr ...[more]

PMID: 24065531

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Project description:BACKGROUND: Aortic dissection(AD) is an acute process of large blood vessels characterized by dangerous pathogenic conditions and high disability and high mortality. The pathogenesis of AD remains debated. Matrix metalloproteinase-12 (MMP-12) participates in many pathological processes such as abdominal aortic aneurysm, atherosclerosis, emphysema and cancer. However, this elastase has rarely been assessed in the presence of AD. The aim of the present study was to investigate the expression of MMP-12 in aortic tissue so as to offer a better understanding of the possible mechanisms of AD. METHODS: The protein expression levels of MMP-12 were analyzed and compared in aorta tissue and the blood serum samples by reverse transcription polymerase chain reaction(RT-PCR), Western blotting, immuno-histochemistry, fluorescence resonance energy transfer ( FRET ) activity assay and enzyme-linked immuno sorbent assay ( ELISA ), respectively. Ascending aorta tissue specimens were obtained from 12 patients with an acute Stanford A-dissection at the time of aortic replacement, and from 4 patients with coronary artery disease (CAD) undergoing coronary artery bypass surgery. Meanwhile, serum samples were harvested from 15 patients with an acute Stanford A-dissection and 10 healthy individuals who served as the control group. RESULTS: MMP-12 activity could be detected in both AD and CAD groups, but the level in the AD group was higher than those in the CAD group (P < 0.05). MMP-12 proteolysis existed in both serum samples of the AD and healthy groups, and the activity level in the AD group was clearly higher than in the healthy group (P < 0.05). For AD patients, MMP-12 activity in serum was higher than in the aorta wall (P < 0.05). MMP-12 activity in the aortic wall tissue can be inhibited by MMP inhibitor v (P < 0.05). CONCLUSION: The present study directly demonstrates that MMP-12 proteolytic activity exists within the aorta specimens and blood samples from aortic dissection patients. MMP-12 might be of potential relevance as a clinically diagnostic tool and therapeutic target in vascular injury and repair.

Project description:BackgroundInflammation may be involved in the pathogenesis of acute aortic dissection (AAD). Toll-like receptor 4 (TLR4) is known to play a critical role in regulating the immune and inflammatory processes. To date, the relationship between genetic variation of TLR4 and AAD is far from clear. The purpose of our study was to illustrate the relevance of TLR4 polymorphisms with the susceptibility to AAD.MethodsA total of 222 AAD patients and 222 controls were enrolled in this study. Frequency distributions of TLR4 polymorphisms (rs10759932 in the promoter and rs11536889 in the 3'-untranslated region) were determined by the KASP method. Clinical parameters were acquired from subjects' medical records, and serum TLR4 levels were collected from our previously published data.ResultsWe found that rs10759932 polymorphism was associated with a reduced risk of AAD in the overall population (CC vs. TT: OR = 0.393, 95%CI = 0.164-0.939, P = 0.036; recessive model: OR = 0.439, 95%CI = 0.196-0.984, P = 0.045) and subgroup analyses stratified by sex. The GC genotype and dominant model of rs11536889 conferred a significantly higher risk of AAD compared with GG genotype in female subjects (GC vs. GG: OR = 3.382, 95%CI = 1.051-10.885, P = 0.041; dominant model: OR = 3.043, 95%CI = 1.041-8.900, P = 0.042). In addition, a significant interaction between the rs11536889 recessive model and dyslipidemia was observed for an increased risk of AAD (P interaction = 0.038, OR = 15.229) after the adjustment for potential clinical covariates. We also used the false-positive report probability (FPRP) analysis to validate the significant results. Furthermore, rs11536889 polymorphism could affect the maximal aortic diameters of AAD (P = 0.037), while AAD patients carrying CC genotype of rs10759932 showed lower serum TLR4 levels than TT genotype carriers (P = 0.043).ConclusionsOur findings provide evidence for the association between TLR4 polymorphisms and AAD susceptibility in a Chinese Han population, which may have some implications for understanding the role of TLR4 in the pathophysiology of AAD.

Dataset Information

Impact of matrix metalloproteinase-8 gene variations on the risk of thoracic aortic dissection in a Chinese Han population.

Publications

Impact of matrix metalloproteinase-8 gene variations on the risk of thoracic aortic dissection in a Chinese Han population.

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