{"id":101580,"date":"2010-11-06T00:00:00","date_gmt":"2010-11-06T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/el-impacto-del-polimorfismo-en-el-codon-72-del-gen-tp53-en-el-pronostico-del-ictus-participacion-de-los-mecanismos-de-muerte-celular-programada\/"},"modified":"2010-11-06T00:00:00","modified_gmt":"2010-11-06T00:00:00","slug":"el-impacto-del-polimorfismo-en-el-codon-72-del-gen-tp53-en-el-pronostico-del-ictus-participacion-de-los-mecanismos-de-muerte-celular-programada","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/genetica-bioquimica\/el-impacto-del-polimorfismo-en-el-codon-72-del-gen-tp53-en-el-pronostico-del-ictus-participacion-de-los-mecanismos-de-muerte-celular-programada\/","title":{"rendered":"El impacto del polimorfismo en el cod\u00f3n 72 del gen tp53 en el pron\u00f3stico del ictus: participaci\u00f3n de los mecanismos de muerte celular programada"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jos\u00e9 Carlos G\u00f3mez S\u00e1nchez <\/strong><\/h2>\n<p>El significado de la apoptosis en el pron\u00f3stico de los pacientes con ictus no es bien conocido. La prote\u00edna supresora tumoral p53 participa en la regulaci\u00f3n de la apoptosis. El polimorfismo del cod\u00f3n 72 del gen tp53(arg72pro) determina la sustituci\u00f3n de arginina por prolina en la prote\u00edna. P53-arg condiciona una mayor susceptibilidad a la apoptosis.  objetivo cl\u00ednico: evaluar arg72pro como marcador pron\u00f3stico en pacientes con infarto cerebral  y en pacientes con hemorragia intracerebral (hic). Objetivo experimental: investigar los mecanismos moleculares que median la diferente actividad apopt\u00f3tica de las variantes polim\u00f3rficas. se estudiaron dos cohortes hospitalarias de pacientes recogiendo variables cl\u00ednicas y genotipando el cod\u00f3n 72. An\u00e1lisis multivariante de regresi\u00f3n log\u00edstica para evaluar predictores independientes de mal pron\u00f3stico. Los mecanismos moleculares se investigaron en cultivos de neuronas corticales. Se expresaron (lipofecci\u00f3n) las variantes humanas: p53-arg o p53-pro, y se analiz\u00f3: apoptosis, actividad de caspasa-3, efecto de inhibidores de caspasas, potencial de membrana mitocondrial y respuesta a estimulaci\u00f3n 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\u00f3stico, frente a 17,3% de los portadores del alelo pro (pro+) (p<0.0001). Tras ajuste multivariante, arg\/arg era marcador de mal pron\u00f3stico (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\u00f3stico en un 92% de arg\/arg frente a 7,9% de los pro+. Arg\/arg tambi\u00e9n era predictor independiente de mal pron\u00f3stico (or: 320; ic 95% 36 - 2786).En cultivos neuronales p53-arg indujo mayor apoptosis neuronal, por activaci\u00f3n de la v\u00eda intr\u00ednseca e interacci\u00f3n con la mitocondria y aument\u00f3 la susceptibilidad a excitotoxicidad y a isquemia. conclusi\u00f3n: el genotipo arg\/arg de tp53 confiere un mayor riesgo de mal pron\u00f3stico tras un ictus y mayor susceptibilidad a la apoptosis neuronal mediada por la mitocondria.\n\n\n\n&nbsp;\n\n\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>El impacto del polimorfismo en el cod\u00f3n 72 del gen tp53 en el pron\u00f3stico del ictus: participaci\u00f3n de los mecanismos de muerte celular programada<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 El impacto del polimorfismo en el cod\u00f3n 72 del gen tp53 en el pron\u00f3stico del ictus: participaci\u00f3n de los mecanismos de muerte celular programada <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jos\u00e9 Carlos G\u00f3mez S\u00e1nchez <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 11\/06\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Rogelio Gonzalez Sarmiento<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Francisco Javier Laso guzman <\/li>\n<li>julio Pascual g\u00f3mez (vocal)<\/li>\n<li>m. mar Castellanos rodrigo (vocal)<\/li>\n<li>Jos\u00e9 Castillo s\u00e1nchez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jos\u00e9 Carlos G\u00f3mez S\u00e1nchez El significado de la apoptosis en el pron\u00f3stico de los pacientes con ictus [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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