Matrix Metalloproteinase 2 Polymorphisms in a Caucasian Population with Abdominal Aortic Aneurysm

Hinterseher, Irene; Bergert, H.; Kuhlisch, Eberhard; Bloomenthal, A.; Pilarsky, Christian; Ockert, D.; Schellong, Sebastian; Saeger, H. D.

doi:10.1016/j.jss.2005.12.001

Cited by 18 publications

(9 citation statements)

References 35 publications

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“…The risk of IUGR occurrence is increased both in CT (OR=3.603, 95% CI=1.577-8.231, p=0.004) and TT carriers (OR=3.391, 95% CI=0.786-14.630, p=0.102), compared to the normal CC genotype. Hinterseher et al, (2006) revealed that the entire coding region and three parts of the promoter of the MMP2 gene failed to show an association between genetic polymorphisms and abdominal aortic aneurysm (AAA). On the other hand, Zhou et al, (2007) observed a 2-fold (OR, 2.12; 95% CI, 1.64-2.72) or 1.6-fold (OR, 1.57; 95% CI, 1.27-1.95) excess risk of developing lung cancer for the -1306CC or -735CC genotype carriers compared with non-carriers, respectively, Miao et al, (2003) found that subjects with the CC genotype had >3-fold increased risk for developing GCA, compared with those with the variant CT or TT genotype, and Yu et al, (2002) demonstrated a significant association between the MMP2 -1306C/T polymorphism and the risk of developing lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Han

Kim

Kang

et al. 2008

Korean J Physiol Pharmacol

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The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and forty two overweight/ obese (BMI ≥ 23) and 145 normal (BMI 18 to ＜ 23) subjects were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used for the analysis of genetic data. A linkage disequilibrium (LD) block was discovered among the 5 SNPs selected, including rs17242319, rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was found to be significantly different. The results suggest that MMP2 may be associated with overweight/obese in Korean population.

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Section: Discussionmentioning

confidence: 99%

Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Han

Kim

Kang

et al. 2008

Korean J Physiol Pharmacol

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“…A study in 51 patients with AAA and 48 controls showed that variations in MMP-2 gene do not contribute to the development of AAA. 307 In contrast, a study enrolling 414 AAA patients and 203 control subjects showed an association between the T allele of the C-1562T functional promoter polymorphism of the MMP-9 gene and AAA formation. 308 Another study enrolling 146 AAA patients and 156 healthy individuals showed no association between MMP-9 and AAA.…”

Section: Mmp Inhibitors As Potential Tools In Pathological Conditionsmentioning

confidence: 94%

Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders

Liu

Khalil

2017

Progress in Molecular Biology and Translational Science

118

161

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Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes that degrade various proteins in the extracellular matrix (ECM). MMPs may also regulate the activity of membrane receptors and post-receptor signaling mechanisms, and thereby affect cell function. The MMP family includes collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs and other MMPs. Inactive proMMPs are cleaved by other MMPs or proteases into active MMPs, which interact with various protein substrates in ECM and cell surface. MMPs regulate important biological processes such as vascular remodeling and angiogenesis, and may be involved in the pathogenesis of cardiovascular disorders such as hypertension, atherosclerosis, and aneurysm. The role of MMPs is often assessed by measuring their mRNA expression, protein levels, and proteolytic activity using gel zymography. MMP inhibitors are also used to assess the role of MMPs in different biological processes and pathological conditions. MMP activity is regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP balance could determine the net MMP activity, ECM turnover, and tissue remodeling. Also, several synthetic MMP inhibitors have been developed. Synthetic MMP inhibitors include a large number of zinc binding globulins (ZBGs), in addition to non-ZBGs and mechanism-based inhibitors. MMP inhibitors have been proposed as potential tools in the management of osteoarthritis, cancer, and cardiovascular disorders. However, most MMP inhibitors have broad-spectrum actions on multiple MMPs and could cause undesirable musculoskeletal side effects. Currently, doxycycline is the only MMP inhibitor approved by the Food and Drug Administration. New generation biological and synthetic MMP inhibitors may show greater MMP specificity and fewer side-effects, and could be useful in targeting specific MMPs, reducing unrestrained tissue remodeling, and the management of MMP-related pathological disorders.

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“…Studies have investigated whether genetic variants of MMPs are associated with AAA risk. A study in 51 patients with AAA and 48 controls showed that variations in MMP-2 gene do not contribute to the development of AAA (Hinterseher et al, 2006). In contrast, a study enrolling 414 AAA patients and 203 control subjects showed an association between the T allele of the C-1562T functional promoter polymorphism of the MMP-9 gene and AAA formation (Jones et al, 2003b).…”

Section: Role Of Mmps In Vascular Pathologymentioning

confidence: 99%

Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease

Wang

Khalil

2018

Advances in Pharmacology

455

316

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that degrade various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs. MMPs are secreted by many cells including fibroblasts, vascular smooth muscle (VSM), and leukocytes. MMPs are regulated at the level of mRNA expression and by activation through removal of the propeptide domain from their latent zymogen form. MMPs are often secreted in an inactive proMMP form, which is cleaved to the active form by various proteinases including other MMPs. MMPs degrade various protein substrates in ECM including collagen and elastin. MMPs could also influence endothelial cell function as well as VSM cell migration, proliferation, Ca signaling, and contraction. MMPs play a role in vascular tissue remodeling during various biological processes such as angiogenesis, embryogenesis, morphogenesis, and wound repair. Alterations in specific MMPs could influence arterial remodeling and lead to various pathological disorders such as hypertension, preeclampsia, atherosclerosis, aneurysm formation, as well as excessive venous dilation and lower extremity venous disease. MMPs are often regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines the extent of ECM protein degradation and tissue remodeling. MMPs may serve as biomarkers and potential therapeutic targets for certain vascular disorders.

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Matrix Metalloproteinase 2 Polymorphisms in a Caucasian Population with Abdominal Aortic Aneurysm

Cited by 18 publications

References 35 publications

Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders

Matrix Metalloproteinases, Vascular Remodeling, and Vascular Disease

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