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dc.contributor.authorSilvestre-Roig, Carlos 
dc.contributor.authorFernandez, Patricia 
dc.contributor.authorMansego, María L
dc.contributor.authorvan Tiel, Claudia M
dc.contributor.authorViana, Rosa
dc.contributor.authorAnselmi, Chiara Viviani
dc.contributor.authorCondorelli, Gianluigi
dc.contributor.authorde Winter, Robbert J
dc.contributor.authorMartín-Fuentes, Paula
dc.contributor.authorSolanas-Barca, María
dc.contributor.authorCiveira, Fernando
dc.contributor.authorFocaccio, Amelia
dc.contributor.authorde Vries, Carlie J M
dc.contributor.authorChaves, Felipe Javier
dc.contributor.authorAndres, Vicente
dc.identifier.citationCirc Cardiovasc Genet. 2014; 7(1):59-70es_ES
dc.description.abstractBACKGROUND: The development of diagnostic tools to assess restenosis risk after stent deployment may enable the intervention to be tailored to the individual patient, for example, by targeting the use of drug-eluting stent to high-risk patients, with the goal of improving safety and reducing costs. The CCNB1 gene (encoding cyclin B1) positively regulates cell proliferation, a key component of in-stent restenosis. Therefore, we hypothesized that single-nucleotide polymorphisms in CCNB1 may serve as useful tools in risk stratification for in-stent restenosis. METHODS AND RESULTS: We identified 3 single-nucleotide polymorphisms in CCNB1 associated with increased restenosis risk in a cohort of 284 patients undergoing coronary angioplasty and stent placement (rs350099: TT versus CC+TC; odds ratio [OR], 1.82; 95% confidence interval [CI], 1.09-3.03; P=0.023; rs350104: CC versus CT+TT; OR, 1.82; 95% CI, 1.02-3.26; P=0.040; and rs164390: GG versus GT+TT; OR, 2.27; 95% CI, 1.33-3.85; P=0.002). These findings were replicated in another cohort study of 715 patients (rs350099: TT versus CC+TC; OR, 1.88; 95% CI, 0.92-3.81; P=0.080; rs350104: CC versus CT+TT; OR, 2.23; 95% CI, 1.18-4.25; P=0.016; and rs164390: GG versus GT+TT; OR, 1.87; 95% CI, 1.03-3.47; P=0.040). Moreover, the haplotype containing all 3 risk alleles is associated with higher CCNB1 mRNA expression in circulating lymphocytes and increased in-stent restenosis risk (OR, 1.43; 95% CI, 1.00-1.823; P=0.039). The risk variants of rs350099, rs350104, and rs164390 are associated with increased reporter gene expression through binding of transcription factors nuclear factor-Y, activator protein 1, and specificity protein 1, respectively. CONCLUSIONS: Allele-dependent transcriptional regulation of CCNB1 associated with rs350099, rs350104, and rs164390 affects the risk of in-stent restenosis. These findings reveal these common genetic variations as attractive diagnostic tools in risk stratification for restenosis.es_ES
dc.description.sponsorshipFina Biotech S.L.U., Ministerio de Economia y Competitividad [SAF2010-16044]; Instituto de Salud Carlos III [RD12/0042/0028, RD12/0042/0055]; Belgian Society of Cardiology; Fundacion Mario Losantos del Campo; Fundacion Ferrer para la Investigacion; BioMedical Materials institute; Dutch Ministry of Economic Affairs; Netherlands Heart Foundation; Ministerio de Economia y Competitividad; Pro-CNIC Foundationes_ES
dc.publisherAmerican Heart Foundationes_ES
dc.subjectAP-1 transcription factores_ES
dc.subjectNF–Y transcription factores_ES
dc.subjectSP1 transcription factores_ES
dc.subjectin-stent restenosises_ES
dc.subjectpolymorphism, geneticses_ES
dc.subject.meshAlleles es_ES
dc.subject.meshCCAAT-Binding Factor es_ES
dc.subject.meshCohort Studies es_ES
dc.subject.meshCoronary Angiography es_ES
dc.subject.meshCoronary Restenosis es_ES
dc.subject.meshCyclin B1 es_ES
dc.subject.meshGenotype es_ES
dc.subject.meshHaplotypes es_ES
dc.subject.meshHumans es_ES
dc.subject.meshKaplan-Meier Estimate es_ES
dc.subject.meshOdds Ratio es_ES
dc.subject.meshPolymorphism, Single Nucleotidees_ES
dc.subject.meshProportional Hazards Models es_ES
dc.subject.meshRNA, Messenger es_ES
dc.subject.meshRisk Factors es_ES
dc.subject.meshSp1 Transcription Factor es_ES
dc.subject.meshTranscription Factor AP-1 es_ES
dc.subject.meshTranscription, Genetices_ES
dc.subject.meshDrug-Eluting Stents es_ES
dc.titleGenetic variants in CCNB1 associated with differential gene transcription and risk of coronary in-stent restenosises_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderBelgian Society of Cardiologyes_ES
dc.contributor.funderFundación Mario Losantos del Campoes_ES
dc.contributor.funderFundación Ferrer para la Investigaciónes_ES
dc.contributor.funderDutch Ministry of Economic Affairses_ES
dc.contributor.funderNetherlands Heart Foundationes_ES
dc.contributor.funderFundación ProCNICes_ES
dc.identifier.journalCirculation. Cardiovascular geneticses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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