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PLoS One. 2013 Aug 9;8(8):e70676. doi: 10.1371/journal.pone.0070676. eCollection 2013.

Pathway analysis using genome-wide association study data for coronary restenosis--a potential role for the PARVB gene.

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1
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

BACKGROUND:

Coronary restenosis after percutaneous coronary intervention (PCI) still remains a significant limitation of the procedure. The causative mechanisms of restenosis have not yet been fully identified. The goal of the current study was to perform gene-set analysis of biological pathways related to inflammation, proliferation, vascular function and transcriptional regulation on coronary restenosis to identify novel genes and pathways related to this condition.

METHODS:

The GENetic DEterminants of Restenosis (GENDER) databank contains genotypic data of 556,099SNPs of 295 cases with restenosis and 571 matched controls. Fifty-four pathways, related to known restenosis-related processes, were selected. Gene-set analysis was performed using PLINK, GRASS and ALIGATOR software. Pathways with a p<0.01 were fine-mapped and significantly associated SNPs were analyzed in an independent replication cohort.

RESULTS:

Six pathways (cell-extracellular matrix (ECM) interactions pathway, IL2 signaling pathway, IL6 signaling pathway, platelet derived growth factor pathway, vitamin D receptor pathway and the mitochondria pathway) were significantly associated in one or two of the software packages. Two SNPs in the cell-ECM interactions pathway were replicated in an independent restenosis cohort. No replication was obtained for the other pathways.

CONCLUSION:

With these results we demonstrate a potential role of the cell-ECM interactions pathway in the development of coronary restenosis. These findings contribute to the increasing knowledge of the genetic etiology of restenosis formation and could serve as a hypothesis-generating effort for further functional studies.

PMID:
23950981
PMCID:
PMC3739784
DOI:
10.1371/journal.pone.0070676
[Indexed for MEDLINE]
Free PMC Article
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