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

Verschuren, Jeffrey J W; Trompet, Stella; Sampietro, M Lourdes; Heijmans, Bastiaan T; Koch, Werner; Kastrati, Adnan; Houwing-Duistermaat, Jeanine J; Slagboom, P Eline; Quax, Paul H A; Jukema, J Wouter

doi:10.1371/journal.pone.0070676

2013

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Document type:: Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Verschuren, Jeffrey J W; Trompet, Stella; Sampietro, M Lourdes; Heijmans, Bastiaan T; Koch, Werner; Kastrati, Adnan; Houwing-Duistermaat, Jeanine J; Slagboom, P Eline; Quax, Paul H A; Jukema, J Wouter
Title:: Pathway analysis using genome-wide association study data for coronary restenosis--a potential role for the PARVB gene.
Abstract:: 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.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.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.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.
Journal title abbreviation:: PLoS ONE
Year:: 2013
Journal volume:: 8
Journal issue:: 8
Pages contribution:: e70676
Language:: eng
Fulltext / DOI:: doi:10.1371/journal.pone.0070676
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/23950981
Print-ISSN:: 1932-6203
TUM Institution:: Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (DHM) (Prof. Schunkert)2013