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Disease Markers
Volume 29, Issue 5, Pages 265-273
http://dx.doi.org/10.3233/DMA-2010-0757

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?

J.J.W. Verschuren,1 M.L. Sampietro,2,10 D. Pons,1,10 S. Trompet,1 M.M. Ewing,3,11 P.H.A. Quax,3,11 P. de Knijff,2 A.H. Zwinderman,4 R.J. de Winter,5,10 R.A. Tio,6,10 M.P. de Maat,7 P.A.F.M. Doevendans,8,10 and J.W. Jukema1,9,10,11

1Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
2Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
3Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
4Department of Medical Statistics, Academic Medical Center, Amsterdam, The Netherlands
5Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
6Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
7Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands
8Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
9Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands
10The Interuniversity Cardiology Institute (ICIN), Utrecht, The Netherlands
11Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

Received 31 December 2010; Accepted 31 December 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Methods and 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.

Conclusion: 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.