Association of functional gene polymorphisms of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐9 with the progression of chronic liver disease

Okamoto, Kinya; Mimura, K.; Murawaki, Yoshikazu; Yuasa, Isao

doi:10.1111/j.1440-1746.2005.03860.x

Cited by 58 publications

(41 citation statements)

References 28 publications

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“…Our data, to a certain extent, can be a helpful supplement for the family-based study, despite having a limited sample size (31 FMMD patients). The MMP-3 5A allele frequency in our controls was 21.2%, which was comparable with the available results in controls (18.9%) from a coronary heart disease study in the Chinese population [37], yet a little bit higher than the frequency in the Japanese population [38]. The inconsistency between the family- and population-based studies might derive from various reasons, and more compelling evidence is needed to clarify this.…”

Section: Discussionsupporting

confidence: 68%

Association of a Functional Polymorphism in the MMP-3 Gene with Moyamoya Disease in the Chinese Han Population

Li¹,

Zhang²,

Liu³

et al. 2010

Cerebrovasc Dis

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Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. The important role of genetic factors in the etiology and pathogenesis of MMD is being increasingly recognized. The study was designed to examine the association of single nucleotide polymorphisms in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) genes with MMD occurrence. Methods: A case-control study was performed. Five functional promoter polymorphisms in the MMP-2, MMP-3, MMP-9 and MMP-13 genes and a potentially functional promoter polymorphism in the TIMP-2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. Their associations with MMD were analyzed by multivariate logistic regression. Results: In total, 208 definite patients with MMD (including 31 familial MMD, FMMD, patients) and 224 healthy subjects were recruited. The frequency of the MMP-3 5A/6A and 5A/5A genotypes was significantly lower in MMD patients (OR = 0.57, 95% CI 0.38–0.86, p_corr = 0.042) compared with healthy controls in a dominant genetic model. Significant differences of the MMP-3 5A/6A polymorphism were also detected between FMMD patients and controls both in the dominant genetic model (OR = 0.23, 95% CI 0.08–0.68, p_corr = 0.048) and the additive genetic model (OR = 0.24, 95% CI 0.08–0.69, p_corr = 0.048). Conclusion: The functional polymorphism in the MMP-3 promoter might be associated with susceptibility to both MMD and FMMD in the Chinese Han population. The findings need to be validated in further studies including more subjects from different populations.

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Section: Discussionsupporting

confidence: 68%

Association of a Functional Polymorphism in the MMP-3 Gene with Moyamoya Disease in the Chinese Han Population

Li¹,

Zhang²,

Liu³

et al. 2010

Cerebrovasc Dis

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“…Of interest, similar results have been found in chronic liver disorders where there were signiWcantly more 2G homozygotes in patients with liver cirrhosis than in patients with chronic hepatitis C virus infection (Okamoto et al 2005). It is well known that the 2G type of SNP at ¡1,607 in the promoter of MMP-1 creates a sequence, 5Ј-GGA-3Ј, that is the core recognition sequence of the binding site for Ets family transcription factors.…”

Section: Discussionmentioning

confidence: 62%

MMP-1 polymorphisms and the risk of idiopathic pulmonary fibrosis

et al. 2008

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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disorder of unknown etiology and unclear pathogenesis. Matrix metalloproteinase-1 (MMP-1) is strongly upregulated and may contribute to the abnormal remodeling that characterizes the disease. We conducted a case-control study of 130 IPF patients and 305 healthy controls to investigate associations between two polymorphisms of the MMP-1 gene promoter and IPF risk. First, using PCR-restriction fragment length polymorphism (PCR-RFLP) analysis we studied the 2G polymorphism at -1,607, shown previously to generate the core of an AP-1 binding site and correlate with high transcriptional activity and risk for IPF. The frequency of the 2G/2G genotype was higher in IPF than in controls (63 vs. 49%; P < 0.008; OR = 1.7; CI 1.15-2.79). Next, we studied a T/G SNP at position -755, which we identified by sequencing the MMP-1 promoter. Chromatin immunoprecipitation (ChIP) assay performed on IPF fibroblasts with either -755 genotype revealed an AP-1 binding site for TT(-755) and GT(-755) genotypes. The frequency of this SNP revealed no significant differences between IPF and healthy controls. However, when the study individuals were stratified by their smoking status, a significant increase in the T/T genotype frequency was observed in smoking cases compared with smoking controls (45 vs. 26%; P = 0.03; OR = 2.3; CI 1.15-4.97). These findings indicate that polymorphisms of the MMP-1 promoter may confer increased risk for IPF and reveal a putative gene-environment interaction between the -755 MMP-1 polymorphism and smoking in this disease.

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“…In another study, the T allele of the -1562 C/T polymorphism was associated with elevated MMP-9 serum levels, but no association with cardiovascular mortality was found [9]. Studies on functional polymorphisms of MMP-9 in patients with pulmonary emphysema [33], abdominal aneurysm [34], end-stage renal disease [35], multiple sclerosis [36], and intracranial aneurysms revealed contradictory results [37,38], In liver disease it has become obvious that MMP-9 may have a very important impact, as illustrated by the predictive value for recurrence of hepatocellular carcinoma after liver transplantation [30], the protection against hepatic I/R injury in MMP-9 deficient/neutralized mice [39,40] and a contribu- Statistical significance X = 11.5; P = 0.001 tion to the progression of chronic liver disease [41]. We found a peak in serum MMP-9 levels at 1 week after OLT in patients with rejection.…”

Section: Discussionmentioning

confidence: 99%

MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

Hove¹,

Rooij²,

Hoek³

et al. 2008

TOTRANSJ

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Abstract:Introduction. Matrix metalloproteinases (MMPs) are involved in connective tissue remodeling processes associated with chronic liver disease and complications after orthotopic liver transplantation (OLT). Genetic variations in the promoter region of the MMP-2 and MMP-9 genes are thought to contribute not only to their transcription rate but may also have predisposing clinical impact. Methods. MMP-2 and MMP-9 gene promoter polymorphisms were analyzed in 109 patients who underwent an OLT. The relationship between these MMP polymorphisms in the donor and recipient DNA with the development of ischemia/reperfusion (I/R) injury and rejection after OLT was evaluated. In addition, serum MMP-2 and MMP-9 levels were determined to illustrate potential phenotypical consequences in these patients. Results. The MMP-2 and -9 genotypes of the donor and recipient or a donor/recipient mismatch and chimerism were not associated with the development of late phase I/R injury or rejection in the OLT patients, although serological differences in the MMP levels did occur. The MMP-2 and -9 genotype distribution did also not have a major impact on the respective serum levels in patients that underwent an OLT. Conclusions. MMP-2 and MMP-9 gene polymorphisms do not seem to contribute to late phase I/R injury or rejection after liver transplantation. Serological changes in the MMP-2 and MMP-9 levels appear to occur independent of the MMP genotype after transplantation of the liver.

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Association of functional gene polymorphisms of matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐9 with the progression of chronic liver disease

Abstract: These findings suggest that MMP-1, MMP-3, and MMP-9 gene polymorphisms account for some of the variability in the progression of HCV-related chronic liver diseases.

Cited by 58 publications

References 28 publications

Association of a Functional Polymorphism in the MMP-3 Gene with Moyamoya Disease in the Chinese Han Population

Association of a Functional Polymorphism in the MMP-3 Gene with Moyamoya Disease in the Chinese Han Population

MMP-1 polymorphisms and the risk of idiopathic pulmonary fibrosis

MMP-2 and MMP-9 Serum Levels Change but their Gene Promoter Polymorphisms are not Associated with Late Phase I/R Injury or Rejection after Orthotopic Liver Transplantation

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