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oai:repisalud.isciii.es:20.500.12105/79172024-09-27T07:55:42Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Silvestre-Roig, Carlos author Fernandez, Patricia author Mansego, María L author van Tiel, Claudia M author Viana, Rosa author Anselmi, Chiara Viviani author Condorelli, Gianluigi author de Winter, Robbert J author Martín-Fuentes, Paula author Solanas-Barca, María author Civeira, Fernando author Focaccio, Amelia author de Vries, Carlie J M author Chaves, Felipe Javier author Andres, Vicente author 2014-02 BACKGROUND: 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. Circ Cardiovasc Genet. 2014; 7(1):59-70 10.1161/CIRCGENETICS.113.000305 1942-3268 1942-325X Circulation. Cardiovascular genetics 24395923 http://hdl.handle.net/20.500.12105/7917 AP-1 transcription factor NF–Y transcription factor SP1 transcription factor In-stent restenosis Polymorphism, genetics Stents Genetic variants in CCNB1 associated with differential gene transcription and risk of coronary in-stent restenosis