{"id":117610,"date":"2015-12-06T00:00:00","date_gmt":"2015-12-06T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/estudio-del-papel-del-polimorfismo-val108-158-met-del-gen-humano-de-la-catecol-o-metiltransferasa-y-su-producto-el-2-metoxiestradiol-en-lel-origen-y-fisiopatologa%c2%ada-de-la-preeclampsia\/"},"modified":"2015-12-06T00:00:00","modified_gmt":"2015-12-06T00:00:00","slug":"estudio-del-papel-del-polimorfismo-val108-158-met-del-gen-humano-de-la-catecol-o-metiltransferasa-y-su-producto-el-2-metoxiestradiol-en-lel-origen-y-fisiopatologa%c2%ada-de-la-preeclampsia","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/ginecologia\/estudio-del-papel-del-polimorfismo-val108-158-met-del-gen-humano-de-la-catecol-o-metiltransferasa-y-su-producto-el-2-metoxiestradiol-en-lel-origen-y-fisiopatologa%c2%ada-de-la-preeclampsia\/","title":{"rendered":"Estudio del papel del polimorfismo val108\/158 met del gen humano de la catecol-o-metiltransferasa y su producto, el 2-metoxiestradiol, en lel origen y fisiopatolog\u00eda de la preeclampsia."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Miriam Pertegal Ruiz <\/strong><\/h2>\n<p>Los objetivos de esta tesis fueron por un lado evaluar la asociaci\u00f3n entre el polimorfismo funcional val108\/158met de la catecol-o-metiltransferasa (comt) fetal y materno y el riesgo de desarrollar preeclampsia (pe), examinando la influencia de dicho polimorfismo en la expresi\u00f3n, la actividad enzim\u00e1tica placentaria de la comt y en los niveles maternos de su producto, el 2-metoxiestradiol (2me), en gestantes control y preecl\u00e1mpticas. Por otra lado, analizamos si los niveles del 2me est\u00e1n relacionados con diferentes \u00edndices de gravedad cl\u00ednica y biomarcadores de la enfermedad.  llevamos a cabo un estudio caso-control observacional, anal\u00edtico y prospectivo en 126 gestantes (53 preecl\u00e1mpticas y 73 gestaciones normales) reclutadas en el hospital cl\u00ednico universitario virgen de la arrixaca de murcia entre enero de 2010 y enero de 2012. Se extrajeron muestras de sangre de las gestantes antes del parto y, una vez producido el mismo, se tom\u00f3 sangre del cord\u00f3n umbilical (fetal) y fragmentos de tejido placentario. Las muestras sangu\u00edneas se utilizaron para realizar los estudios de genotipado, y para medir los niveles maternos de 2me, y de diferentes biomarcadores relacionados con la pe (homociste\u00edna, sflt1, plgf). Por otra parte, en el tejido placentario se realizaron los an\u00e1lisis de expresi\u00f3n y actividad enzim\u00e1tica de la comt. Finalmente, obtuvimos datos cl\u00ednicos y anal\u00edticos de la historia cl\u00ednica de las pacientes.  los principales resultados de este trabajo muestran que el genotipo met-met fue el doble de frecuente en la sangre fetal de gestantes preecl\u00e1mpticas que en las controles. La odds ratio ajustada (orajt) para el riesgo de pe en dichas mujeres fue de 3.22 [intervalo de confianza (ic) 95%: 1.01, 10.28]. Los an\u00e1lisis del polimorfismo materno de la comt no revelaron un aumento significativo del riesgo de pe, y tampoco a\u00f1adi\u00f3 nada el estudio de los haplotipos de la comt. Al analizar la actividad enzim\u00e1tica in vitro, \u00e9sta se vio determinada por el polimorfismo fetal val108\/158met, siendo menor para el genotipo met-met que para el val-met y el val-val tanto en  poblaci\u00f3n total como en la preecl\u00e1mptica. La actividad de la comt in vitro no difiri\u00f3 entre controles y preecl\u00e1mpticas dentro de cada genotipo. En cuanto a la expresi\u00f3n de la comt soluble, \u00e9sta fue menor para el genotipo met-met en ambas subpoblaciones y dicha expresi\u00f3n se correlacion\u00f3 inversamente con los valores de actividad in vitro, pudiendo por tanto estar determinada dicha actividad por la cantidad de prote\u00edna. La expresi\u00f3n placentaria de la comt soluble no difiri\u00f3 entre controles y preecl\u00e1mpticas dentro de cada genotipo. En lo que respecta a la actividad in vivo, no encontramos ninguna asociaci\u00f3n entre el polimorfismo estudiado y los niveles de 2me en plasma materno; no obstante los valores de 2me s\u00ed estuvieron significativamente disminuidos en las gestantes con pe frente a las controles (1818.41\u00c2\u00b1189.25 pg\/ml vs 2906.43\u00c2\u00b1200.69 pg\/ml). Adem\u00e1s, las gestantes con pe presentaron unos niveles plasm\u00e1ticos mayores de homociste\u00edna, condicionando \u00e9stos un mayor riesgo de pe, y correlacion\u00e1ndose inversamente con los valores de 2me, lo que podr\u00eda contribuir a la menor actividad observada de la comt in vivo en pe. Por otra parte, los valores plasm\u00e1ticos de 2me se correlacionaron con par\u00e1metros cl\u00ednicos y anal\u00edticos de gravedad del s\u00edndrome como la mayor tensi\u00f3n arterial sist\u00f3lica pico, la necesidad de una mayor agresividad terap\u00e9utica antihipertensiva, el menor peso neonatal o la precocidad de la pe. Finalmente, los niveles maternos de 2me tambi\u00e9n se correlacionaron, tanto en la poblaci\u00f3n total como en la preecl\u00e1mptica, con conocidos factores de desequilibrio angiog\u00e9nico en pe como el sflt1 o el plgf, sugiriendo que el 2me podr\u00eda ser un factor clave en el mantenimiento del equilibrio angiog\u00e9nico necesario para el correcto desarrollo de la gestaci\u00f3n.    the objectives of this thesis were on one hand to assess the association between fetal and maternal catechol-o-methyltransferase (comt) val108\/158met functional polymorphism and the risk of developing preeclampsia (pe), examining the influence of this polymorphism in expression and activity of placental comt enzyme and in maternal plasma levels of its product, 2-methoxyestradiol (2me), in both control and preeclamptic pregnant women. On the other hand, we analyze whether 2me levels are associated with different clinical severity index and biomarkers of pe. we conducted an observational, analytical and prospective case-control study in 126 pregnant women (53 preeclamptic and 73 normal pregnancies) recruited at the hospital cl\u00ednico universitario virgen de la arrixaca in murcia from january 2010 to january 2012. Blood samples of pregnant women were taken before delivery and, immediately after, cord blood (fetal) and placental tissue fragments were taken. Blood samples were used for genotyping studies, and to measure maternal levels of 2me, and different biomarkers related to pe (homocysteine, sflt1, plgf). Moreover, we made the analysis of expression and enzymatic activity in vitro of comt in placental tissue. Finally, we obtained clinical and laboratory data from the clinical history of patients. the main results of this work show that the genotype met-met was twice as frequent in fetal blood from patients with pe as in controls. The adjusted odds ratio (orajt) for the risk of pe in these women was 3.22 [95% confidence interval (ci): 1.01 -10.28]. Analyses of maternal comt polymorphism did no reveal a significant increased risk of pe, and either added nothing comt haplotypes analysis. When analyzing the enzyme activity in vitro, it was determined by fetal val108\/158met polymorphism, being lower for met-met genotype than for val-met and val-val both the total population and preeclamptic. The comt activity in vitro did not differ between control and preeclamptic pregnant women within each genotype. The expression of soluble comt was lower for the met-met genotype in both subpopulations and this expression was inversely correlated with in vitro activity values, then such activity may be determined by the amount of protein. Placental expression of soluble comt not differ between controls and preeclamptic within each genotype in respect to in vivo activity, we found no association between the polymorphism studied and levels of 2me in maternal plasma, however those values were significantly decreased in women with pe compared to control (1818.41\u00c2\u00b1189.25 pg\/ml versus 2906.43\u00c2\u00b1200.69 pg\/ml). In addition, there were a higher plasma homocysteine levels in preeclamptic women conditioning them at increased risk of pe, and correlated inversely with the values of 2me in total population, which could contribute to the lower comt activity in vivo observed in pe. On the other hand, plasmatic 2me values were significantly correlated with different clinical and laboratory parameters of severity of the syndrome such as higher peak systolic blood pressure, the need for more aggressive antihypertensive therapeutic, lower birth weight or early onset of pe. Finally, maternal 2me levels were also correlated (in patients with pe and in total population) with known angiogenic imbalance factors present in pe as sflt1 or plgf, suggesting that 2me could be a key factor in maintaining the balance angiogenic necessary for the proper development of gestation.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Estudio del papel del polimorfismo val108\/158 met del gen humano de la catecol-o-metiltransferasa y su producto, el 2-metoxiestradiol, en lel origen y fisiopatolog\u00eda de la preeclampsia.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Estudio del papel del polimorfismo val108\/158 met del gen humano de la catecol-o-metiltransferasa y su producto, el 2-metoxiestradiol, en lel origen y fisiopatolog\u00eda de la preeclampsia. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Miriam Pertegal Ruiz <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Murcia<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 12\/06\/2015<\/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>Isabel Hernandez Garcia<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: alfredo Perales mar\u00edn <\/li>\n<li>m. Jos\u00e9 Garcia teruel (vocal)<\/li>\n<li>anibal Nieto diaz (vocal)<\/li>\n<li>francesc Figueras retuerta (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Miriam Pertegal Ruiz Los objetivos de esta tesis fueron por un lado evaluar la asociaci\u00f3n entre el [&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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[5793,135,8235],"tags":[29063,154731,52732,102960,175406,231662],"class_list":["post-117610","post","type-post","status-publish","format-standard","hentry","category-fisiologia-cardiovascular","category-ginecologia","category-murcia","tag-alfredo-perales-marin","tag-anibal-nieto-diaz","tag-francesc-figueras-retuerta","tag-isabel-hernandez-garcia","tag-m-jose-garcia-teruel","tag-miriam-pertegal-ruiz"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/117610","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=117610"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/117610\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=117610"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=117610"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=117610"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}