title: 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: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trine B
authors.initials: TB
authors.lastname: Opstad
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Alf Å
authors.initials: AÅ
authors.lastname: Pettersen
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications* / Q000235:genetics*; D003596:Cytosine / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013941:Thymine / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D003596:Cytosine; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013941:Thymine