title: Genetic variation, gene-expression and circulating levels of matrix metalloproteinase-9 in patients with stable coronary artery disease.
abstract: BACKGROUND
  Mediators involved in atherosclerosis and plaque rupture may have importance as risk markers for coronary artery disease (CAD). We have investigated the influence of matrix metalloproteinase (MMP)-9 genetic variations on gene- and protein expression in stable CAD patients.
  
  
  METHODS
  The promoter -1562C/T and exon 6 R279Q A/G polymorphisms were determined in 1001 patients with angiographically verified stable CAD and in 204 healthy controls. Genotype and gene-expression were determined by real-time PCR. Serum levels of MMP-9 and its inhibitor TIMP-1were measured immunologically and by zymography (MMP-9 activity).
  
  
  RESULTS
  None of the polymorphisms associated with the presence of CAD, myocardial infarction or type 2 diabetes, whereas the variant allele of the R279Q polymorphism associated with hypertension (adjusted p=0.015). The T- and G alleles associated with lower and higher mRNA levels, respectively (p<0.005 both), also shown in an experimental ex-vivo LPS stimulated model. T-allele carriers had higher concentrations of MMP-9 (adjusted p=0.032) and the GG genotype induced lower MMP-9 gelatinolytic activity (p=0.01). Higher MMP-9 gene-expression and TIMP-1 levels were observed in patients with previous myocardial infarction, the latter also was elevated in diabetics (<0.05, all).
  
  
  CONCLUSIONS
  The investigated MMP-9 polymorphisms influenced gene- and protein expression differently and the R279Q polymorphism associated significantly with hypertension.
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ulleval, Norway. trineoa@medisin.uio.no
authors.forename: Trine B
authors.initials: TB
authors.lastname: Opstad
authors.forename: Alf-Aage R
authors.initials: AA
authors.lastname: Pettersen
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Weiss
authors.forename: Sissel
authors.initials: S
authors.lastname: Akra
authors.forename: Reidun
authors.initials: R
authors.lastname: Øvstebø
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology*; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9