Dataset Information

MMP-2 gene polymorphisms are associated with type A aortic dissection and aortic diameters in patients.

ABSTRACT: Matrix metalloproteinases-2 (MMP-2) plays an important role in the pathogenesis of type A aortic dissection (AD). The aim of this study was to evaluate the association of 3 single nucleotide polymorphisms (SNPs) in the MMP-2 gene with type A AD risk and aortic diameters in patients. We performed a case-control study with 172 unrelated type A AD patients and 439 controls. Three SNPs rs11644561, rs11643630, and rs243865 were genotyped through the MassARRAY platform. Allelic associations of SNPs and SNP haplotypes with type A AD and aortic diameters in patients were evaluated. The frequency of the G allele of the rs11643630 polymorphism was significantly lower in type A AD patients than in control subjects (odds ratio 0.705, 95% confidence interval 0.545-0.912, P?=?0.008). The association remained significant after adjusting for clinical covariates (P?=?0.008). Carriers of the GG genotype of the rs11643630 polymorphism had significantly smaller aortic diameters than those with GT genotype or TT genotype (P?=?0.02). Further haplotype analysis identified 1 protective haplotype (GC; P?=?0.008) for development of type A AD. Again, a significant correlation was observed between haplotype GC and AD size (P?=?0.020). Our results suggest that MMP-2 gene polymorphisms contribute to type A AD susceptibility. In addition, MMP-2 gene SNPs are associated with AD size, which could be used as a target for the development of new drug therapy.

SUBMITTER: Liu O

PROVIDER: S-EPMC5079335 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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MMP-2 gene polymorphisms are associated with type A aortic dissection and aortic diameters in patients.

Liu Ou O Xie Wuxiang W Qin Yanwen Y Jia Lixin L Zhang Jing J Xin Yi Y Guan Xinliang X Li Haiyang H Gong Ming M Liu Yuyong Y Wang Xiaolong X Li Jianrong J Lan Feng F Zhang Hongjia H

Medicine 20161001 42

Matrix metalloproteinases-2 (MMP-2) plays an important role in the pathogenesis of type A aortic dissection (AD). The aim of this study was to evaluate the association of 3 single nucleotide polymorphisms (SNPs) in the MMP-2 gene with type A AD risk and aortic diameters in patients. We performed a case-control study with 172 unrelated type A AD patients and 439 controls. Three SNPs rs11644561, rs11643630, and rs243865 were genotyped through the MassARRAY platform. Allelic associations of SNPs an ...[more]

PMID: 27759651

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Project description:ObjectiveAcute aortic dissection is a life-threatening condition. Thoracic endovascular aortic repair (TEVAR), together with optimized medical treatment, is currently the first line treatment for acute Stanford type B aortic dissection. TEVAR can close the entry tear and reduce mortality. Aortic remodeling after TEVAR can directly affect the patient's long-term prognosis. The factors that influence aortic remodeling have, however, received insufficient clinical attention and remain unclear. It is very important to identify these factors.MethodsA total of 100 patients were continuously enrolled from 2011 to 2018 in 2 centers. Relevant data, including time from hospital admission to surgery, medicine use and aortic computed tomography angiography images obtained before and 6 months after surgery were collected. Patients were divided into favorable and adverse aortic remodeling groups, according to the degree of aortic remodeling. Analysis of variance and the chi-square test were performed using SPSS software to compare differences between groups and to determine the factors that influence postoperative aortic remodeling.ResultsThe proportion of single-stent implantations was higher in the favorable remodeling group than in the adverse remodeling group (79.5% vs. 53.8% in distal end of stent-graft level and 81.3% vs. 56.4% in diaphragm level, respectively, p < 0.05). The earlier the TEVAR procedure was performed, the better the aortic remodeling (3.4 days vs. 4.8 days in distal stent graft levels, and 3.6 days vs. 4.9 days in diaphragm level, respectively, p < 0.05), the presence of residual distal entry tears in the abdominal aorta also improved aortic remodeling after TEVAR (85.7% vs. 55.1% in the celiac trunk level, and 92.0% vs. 48.9% in the right renal artery level, respectively, p < 0.05).ConclusionSingle stent-graft implantation and early surgery were associated with favorable aortic remodeling. Distal entry tears were also conducive to aortic remodeling after surgery for aortic dissection.

Project description:Background This study compared left ventricular (LV) characteristics between patients with type-A and type-B aortic dissection (AD) and evaluated the ability of LV remodeling phenotypes (hypertrophy, concentricity, or geometric patterns) to predict mortality in both AD types. Methods and Results We evaluated 236 patients with type A and 120 patients with type B who had echocardiograms within 60 days before or after AD diagnosis (median [25th, 75th percentiles] time difference between echocardiogram and AD diagnosis=1 [0, 6] days) from 3 centers. Patients were stratified according to LV phenotypes, and early (90-day) and late (1-year) mortality after AD diagnosis were assessed. In adjusted logistic regression analysis, patients with type A had higher and lower odds of concentric and eccentric hypertrophy (odds ratio [OR], 2.56; 95% CI, 1.50-4.36; P<0.001; and OR, 0.55; 95% CI, 0.31-0.97; P=0.039, respectively) than those with type B. Results of multivariable Cox-regression analysis showed that LV remodeling phenotypes were not related to mortality in patients with type B. By contrast, LV concentricity was associated with greater early and late mortality (hazard ratio [HR], 2.22; 95% CI, 1.24-3.96; P=0.007 and HR, 2.06; 95% CI, 1.20-3.54; P=0.009, respectively) in type A. In further analysis considering normal LV geometry as reference, LV concentric remodeling and concentric hypertrophy were associated with early mortality (HR, 7.78; 95% CI, 2.35-25.78; P<0.001 and HR, 4.38; 95% CI, 1.47-13.11; P=0.008, respectively), whereas concentric remodeling was associated with late mortality (HR, 5.40; 95% CI, 1.91-15.26; P<0.001) among patients with type A. Assessment of LV geometric patterns and concentricity provided incremental prognostic value in predicting early and late mortality beyond clinical variables in patients with type A based on net reclassification improvement and integrated discrimination improvement. Conclusions LV geometric patterns derived from LV concentricity were associated with greater mortality among patients with type A and may be markers of adverse prognosis in this population.

Project description:Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear. Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein-protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm. Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell-cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group. Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.

Dataset Information

MMP-2 gene polymorphisms are associated with type A aortic dissection and aortic diameters in patients.

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MMP-2 gene polymorphisms are associated with type A aortic dissection and aortic diameters in patients.

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