Pathway Analysis Using Genome-Wide Association Study Data for Coronary Restenosis – A Potential Role for the PARVB Gene
| Autor: | P. Eline Slagboom, Jeffrey J. W. Verschuren, Werner Koch, J. Wouter Jukema, Stella Trompet, Jeanine J. Houwing-Duistermaat, Adnan Kastrati, Bastiaan T. Heijmans, M. Lourdes Sampietro, Paul H.A. Quax |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Platelet-derived growth factor Epidemiology medicine.medical_treatment Genome-wide association study 030204 cardiovascular system & hematology Cardiovascular Bioinformatics Calcitriol receptor chemistry.chemical_compound 0302 clinical medicine Restenosis Actinin 0303 health sciences Multidisciplinary Genomics Middle Aged Interventional Cardiology Extracellular Matrix Genetic Epidemiology Cytokines Medicine Female Signal transduction Metabolic Networks and Pathways Signal Transduction Research Article Science Single-nucleotide polymorphism Coronary Restenosis Biological pathway 03 medical and health sciences Genome Analysis Tools Vascular Biology Genome-Wide Association Studies Genetics medicine Humans Genetic Predisposition to Disease Biology Genetic Association Studies Aged 030304 developmental biology Evolutionary Biology Population Biology business.industry Endothelial Cells Computational Biology Percutaneous coronary intervention Human Genetics medicine.disease Gene Expression Regulation chemistry Case-Control Studies Genetic Polymorphism Endothelium Vascular business Software Population Genetics Genome-Wide Association Study |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 8, p e70676 (2013) PLoS ONE, 8(8) PLoS ONE; Vol 8 |
| ISSN: | 1932-6203 |
| Popis: | BackgroundCoronary 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.MethodsThe 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 pResultsSix 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.ConclusionWith 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. |
| Databáze: | OpenAIRE |
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