title: Matrix metalloproteinases 2 and 3 gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention: Is there still room for determining genetic variation of MMPs for assessment of an increased risk of restenosis?
abstract: OBJECTIVE
  Mixed results have been reported of matrix metalloproteinases (MMP) and their association with restenosis after percutaneous coronary intervention (PCI). The current study examines whether multiple single nucleotide polymorphisms (SNPs), covering the full genomic region of MMP2 and MMP3, were associated with restenosis in the GENDER study population.
  
  
  RESULTS
  The GENetic DEterminants of Restenosis (GENDER) study enrolled 3104 consecutive patients after successful PCI. The primary endpoint was clinical restenosis, defined as target vessel revascularization (TVR), occurring in 9.8% of the patients. From the Hapmap database, 19 polymorphisms of MMP2 and 11 of MMP3 were selected. Furthermore, in a subpopulation, a genome-wide association analysis (GWA) was performed. No significant association was found with any of the investigated SNPs, including the previously reported 5A/6A polymorphism (rs3025058), with regard to TVR using single SNP analysis or haplotype analysis.
  
  
  CONCLUSIONS
  We found no significant association of MMP2 or MMP3 with TVR with this SNP-broad gene approach. Although we did not test all the known polymorphisms of these genes, using tagging analyses we examined those SNPs covering all known haplotypes of MMP2 and MMP3 to conclude that these genes do not correlate with a genetic risk of coronary restenosis after successful PCI.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J J W
authors.initials: JJ
authors.lastname: Verschuren
authors.forename: M L
authors.initials: ML
authors.lastname: Sampietro
authors.forename: D
authors.initials: D
authors.lastname: Pons
authors.forename: S
authors.initials: S
authors.lastname: Trompet
authors.forename: M M
authors.initials: MM
authors.lastname: Ewing
authors.forename: P H A
authors.initials: PH
authors.lastname: Quax
authors.forename: P
authors.initials: P
authors.lastname: de Knijff
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: R J
authors.initials: RJ
authors.lastname: de Winter
authors.forename: R A
authors.initials: RA
authors.lastname: Tio
authors.forename: M P
authors.initials: MP
authors.lastname: de Maat
authors.forename: P A F M
authors.initials: PA
authors.lastname: Doevendans
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D001483:Base Sequence; D016022:Case-Control Studies; D023903:Coronary Restenosis / Q000453:epidemiology / Q000235:genetics*; D023921:Coronary Stenosis / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D009204:Myocardial Revascularization; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2