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The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

ABSTRACT: Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 -1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 -1562 C/T polymorphism in subjects with CAD and MetS.Patients (n?=?1000) with verified CAD stratified in Mets +/- (n?=?244/756), were analyzed for the MMP-9 -1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients.Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p?=?0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001).In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.

SUBMITTER: Opstad TB

PROVIDER: S-EPMC4156385 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

Opstad Trine B TB Arnesen Harald H Pettersen Alf Å AÅ Seljeflot Ingebjørg I

PloS one 20140905 9

<h4>Background and objectives</h4>Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 -1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 -1562 C/T polymorphism in subjects with CAD and MetS.<h4>Methods</h4>Patients (n = 1000) with verifi ...[more]

PMID: 25191702

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Project description:IntroductionMatrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected.Materials and methodsA case-control study exploratory was carried out in a cohort of infected patients. 540 individuals were selected in total, 270 patients with sepsis and 270 controls (infected but non-septic), classified according to the 2016 consensus (Sepsis-3). The presence of the single-nucleotide polymorphism (SNP; allele T and/or allele C) was determined through analyses of restriction fragment length polymorphism and plasma levels of MMP-9 were determined through enzyme-linked immunosorbent assay immunoassay.ResultsSNP MMP-9 -1562 has two known alleles (T and C), with predominance of the C over the T allele; in the group of patients with sepsis, T allele was found in 7.2% of cases, while C allele in the rest (92.8%); in comparison, in the group of infected but non-septic patients, frequencies were 9.4% for T allele and 90.6% for the C allele (P = .33). Also, the presence of the polymorphic T allele was not related to the levels of MMP-9 in patients with sepsis in comparison with infected but non-septic patients 780 (397-1375) ng/mL vs 646 (172-1249) ng/mL (P = .64). There was also no association between the SNP and sepsis mortality (P = .78).ConclusionsWe concluded that there was no association between the SNP MMP9 -1562 C/T and sepsis or between the SNP MMP9 -1562 C/T and sepsis mortality in the Northeastern Colombian septic patient cohort. Further research is needed to clarify the correlation among sepsis, genetic factors with allele T and MMP-9 plasma concentration.

Project description:BackgroundAlthough many studies have focused on the association of the MMP-9 promoter -1562 C/T polymorphism with the susceptibility and/or severity of chronic periodontitis (CP), results have been inconsistent. Therefore, a meta-analysis of all eligible studies was performed to derive a more precise estimation of the association between this polymorphism and CP risk.MethodsAll relevant studies were identified through a database search in PubMed, Medline, and Web of Science. All the full-text studies with appropriate analytical design, published in English, which evaluated the association of MMP-9 promoter -1562C/T polymorphism with CP risk using validated genotyping methods, and with non-duplicated data were selected for this study. A fixed-effect model was used to calculate pooled ORs in the absence of heterogeneity across included trials (P > 0.1 and I(2) < 50 %), otherwise the random-effect model was applied.ResultsIn an overall meta-analysis, pooled ORs revealed that T variant in the MMP-9 promoter -1562 C/T polymorphism was associated with a significantly decreased risk for CP under all comparison models. In subgroup analyses by ethnicity, pooled ORs showed that a significant association of the MMP-9 promoter -1562 C/T polymorphism with CP risk was only detected in Caucasians and Asians but not in mixed population. In the subgroup analysis by severity of CP, pooled ORs indicated that T allele of the MMP-9 promoter -1562 C/T polymorphism was associated with decreased susceptibility to severe CP while there was no significant association between this polymorphism and moderate CP.ConclusionsOur meta-analysis showed that T allele in the MMP-9 promoter -1562 C/T polymorphism might be a protective factor for CP, especially in Caucasians and Asians. Moreover, there was a significant association of the MMP-9 promoter -1562 C/T polymorphism with decreased susceptibility to severe CP, while the allelic and/or genotype distributions of this polymorphism were not associated with moderate CP.

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The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

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The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

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