p27kip1-838C>A single nucleotide polymorphism is associated with restenosis risk after coronary stenting and modulates p27kip1 promoter activity.
Circulation
; 120(8): 669-76, 2009 Aug 25.
Article
em En
| MEDLINE
| ID: mdl-19667240
ABSTRACT
BACKGROUND:
The cyclin-dependent kinase inhibitor p27(kip1) is a key regulator of smooth muscle cell and leukocyte proliferation in vascular disease, including in-stent restenosis. We therefore hypothesized that common genetic variations or single nucleotide polymorphisms in p27(kip1) may serve as a useful tool in risk stratification for in-stent restenosis. METHODS ANDRESULTS:
Three single nucleotide polymorphisms concerning the p27(kip1) gene (-838C>A, rs36228499; -79C>T, rs34330; +326G>T, rs2066827) were determined in a cohort of 715 patients undergoing coronary angioplasty and stent placement. We discovered that the p27(kip1)-838C>A single nucleotide polymorphism is associated with clinical in-stent restenosis; the -838AA genotype decreases the risk of target vessel revascularization (hazard ratio, 0.28; 95% confidence interval, 0.10 to 0.77). This finding was replicated in another cohort study of 2309 patients (hazard ratio, 0.61; 95% confidence interval, 0.40 to 0.93). No association was detected between this end point and the p27(kip1)-79C>T and +326G>T single nucleotide polymorphisms. We subsequently studied the functional importance of the -838C>A single nucleotide polymorphism and detected a 20-fold increased basal p27(kip1) transcriptional activity of the -838A allele containing promoter.CONCLUSIONS:
Patients with the p27(kip1)-838AA genotype have a decreased risk of in-stent restenosis corresponding with enhanced promoter activity of the -838A allele of this cell-cycle inhibitor, which may explain decreased smooth muscle cell proliferation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
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Reestenose Coronária
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Peptídeos e Proteínas de Sinalização Intracelular
Tipo de estudo:
Etiology_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Circulation
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Holanda