Systematic testing of literature reported genetic variation associated with coronary restenosis: results of the GENDER Study

PLoS One. 2012;7(8):e42401. doi: 10.1371/journal.pone.0042401. Epub 2012 Aug 3.

Abstract

Background: Coronary restenosis after percutaneous coronary intervention still remains a significant problem, despite all medical advances. Unraveling the mechanisms leading to restenosis development remains challenging. Many studies have identified genetic markers associated with restenosis, but consistent replication of the reported markers is scarce. The aim of the current study was to analyze the joined effect of previously in literature reported candidate genes for restenosis in the GENetic DEterminants of Restenosis (GENDER) databank.

Methodology/principal findings: Candidate genes were selected using a MEDLINE search including the terms 'genetic polymorphism' and 'coronary restenosis'. The final set included 36 genes. Subsequently, all single nucleotide polymorphisms (SNPs) in the genomic region of these genes were analyzed in GENDER using set-based analysis in PLINK. The GENDER databank contains genotypic data of 2,571,586 SNPs of 295 cases with restenosis and 571 matched controls. The set, including all 36 literature reported genes, was, indeed, significantly associated with restenosis, p = 0.024 in the GENDER study. Subsequent analyses of the individual genes demonstrated that the observed association of the complete set was determined by 6 of the 36 genes.

Conclusion: Despite overt inconsistencies in literature, with regard to individual candidate gene studies, this is the first study demonstrating that the joint effect of all these genes together, indeed, is associated with restenosis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Restenosis / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Sex Characteristics

Grants and funding

This work was funded by grants from the Interuniversity Cardiology Institute of the Netherlands (ICIN) http://www.icin.nl/, the European Community Framework FP7 Programme under grant agreement [n° HEALTH-F2-2009-223004; http://cordis.europa.eu/projects/90569_en.html], the Center for Medical Systems Biology (CMSB) [http://www.cmsb.nl], a center of excellence approved by the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research (NWO), and the Netherlands Consortium for Healthy Ageing (NCHA) [http://www.healthy-ageing.nl]. JWJ is an established clinical investigator of the Netherlands Heart Foundation (2001D032) [http://www.hartstichting.nl/]. The funders had no role in study design, data collection and analysis, decision to publish or the preparation of the manuscript.