[en] The significance of apoptosis in the prognosis of stroke patients is not well known. The p53 tumor suppressor protein involved in regulation of apoptosis. The polymorphism at codon 72 of TP53 gene (Arg72Pro) determines the substitution of arginine for proline in the protein. p53-Arg conditions increased susceptibility to apoptosis. Clinical objective: to assess Arg72Pro as a prognostic marker in patients with cerebral infarction and in patients with intracerebral hemorrhage (ICH). Experimental Objective: To investigate the molecular mechanisms that mediate the apoptotic activity of different polymorphic variants. We studied two cohorts of patients collecting hospital clinical and codon 72 genotyping. Multivariate logistic regression to assess independent predictors of poor prognosis. The molecular mechanisms were investigated in cultured cortical neurons. Were expressed (lipofection) human variants: p53 or p53-Arg-Pro, and analyzed for: apoptosis, caspase-3 activity, effect of caspase inhibitors, mitochondrial membrane potential and response to stimulation with glutamate and experimental ischemia. Results: 408 patients with stroke: 57.6% Arg / Arg, 36% Arg / Pro and 6.4% Pro / Pro. 55.7% of patients Arg / Arg had a poor prognosis, compared with 17.3% of the Pro allele carriers (Pro +) (p <0.0001). After multivariate adjustment, Arg / Arg was a marker of poor prognosis (OR: 3.4, 95% CI 1.54 to 7.61). 128 patients with ICH: 52.3% Arg / Arg, 42.2% Arg / Proj 5.5% Pro / Pro. Poor prognosis in 92% Arg / Arg versus 7.9% of the Pro +. Arg / Arg was also an independent predictor of poor prognosis (OR: 320, 95% CI 36-2786). In neuronal cultures induced p53-Arg increased neuronal apoptosis, activation of the intrinsic pathway and interaction with the mitochondria and increased susceptibility to excitotoxicity and ischemia. Conclusion: The genotype Arg / Arg of Tp53 confers an increased risk of poor outcome after stroke and increased susceptibility to neuronal apoptosis mediated by mitochondria.

[es] El significado de la apoptosis en el pron?stico de los pacientes con ictus no es bien conocido. La prote?na supresora tumoral p53 participa en la regulaci?n de la apoptosis. El polimorfismo del cod?n 72 del gen Tp53(Arg72Pro) determina la sustituci?n de arginina por prolina en la prote?na. p53-Arg condiciona una mayor susceptibilidad a la apoptosis. Objetivo cl?nico: evaluar Arg72Pro como marcador pron?stico en pacientes con infarto cerebral y en pacientes con hemorragia intracerebral (HIC). Objetivo experimental: investigar los mecanismos moleculares que median la diferente actividad apopt?tica de las variantes polim?rficas. Se estudiaron dos cohortes hospitalarias de pacientes recogiendo variables cl?nicas y genotipando el cod?n 72. An?lisis multivariante de regresi?n log?stica para evaluar predictores independientes de mal pron?stico. Los mecanismos moleculares se investigaron en cultivos de neuronas corticales. Se expresaron (lipofecci?n) las variantes humanas: p53-Arg o p53-Pro, y se analiz?: apoptosis, actividad de caspasa-3, efecto de inhibidores de caspasas, potencial de membrana mitocondrial y respuesta a estimulaci?n con glutamato y a isquemia experimental. Resultados: 408 pacientes con infarto cerebral: 57,6% Arg/Arg, 36% Arg/Pro y 6,4% Pro/Pro. 55,7% de los pacientes Arg/Arg tuvieron mal pron?stico, frente a 17,3% de los portadores del alelo Pro (Pro+) (p<0.0001). Tras ajuste multivariante, Arg/Arg era marcador de mal pron?stico (OR: 3,4; IC 95% 1,54 - 7,61). 128 pacientes con HIC: 52,3% Arg/Arg, 42,2% Arg/Proy 5,5% Pro/Pro. Mal pron?stico en un 92% de Arg/Arg frente a 7,9% de los Pro+. Arg/Arg tambi?n era predictor independiente de mal pron?stico (OR: 320; IC 95% 36 - 2786).En cultivos neuronales p53-Arg indujo mayor apoptosis neuronal, por activaci?n de la v?a intr?nseca e interacci?n con la mitocondria y aument? la susceptibilidad a excitotoxicidad y a isquemia. Conclusi?n: El genotipo Arg/Arg de Tp53 confiere un mayor riesgo de mal pron?stico tras un ictus y mayor susceptibilidad a la apoptosis neuronal mediada por la mitocondria.