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Hay datos convincentes de que la ET-1 desempe&#241;a un papel importante en la patogenia de la proteinuria y la glomeruloesclerosis mediante la activaci&#243;n del receptor de la ET-1 tipo A&#44; que produce estr&#233;s oxidativo y da&#241;a las c&#233;lulas endoteliales adyacentes del glom&#233;rulo renal mediante un mecanismo paracrino que tambi&#233;n causa un da&#241;o rec&#237;proco a los podocitos<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Varios estudios han analizado la asociaci&#243;n entre el polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la hipertensi&#243;n&#44; la presi&#243;n arterial sist&#243;lica y el nivel de colesterol de las lipoprote&#237;nas de alta densidad&#44; aunque con resultados contradictorios<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6-11</span></a>&#46; Con relaci&#243;n a las nefropat&#237;as&#44; las variantes del gen <span class="elsevierStyleItalic">EDN1</span> se han asociado con la progresi&#243;n de la enfermedad renal poliqu&#237;stica autos&#243;mica dominante<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> y la nefropat&#237;a IgA<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a>&#46; Los estudios que analizan el impacto de los polimorfismos del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN son escasos<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a>&#46; El objetivo principal de nuestro estudio fue establecer los genotipos y frecuencias al&#233;licas del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN primario&#46; Tambi&#233;n se analiz&#243; la asociaci&#243;n entre las variantes de este polimorfismo de un solo nucle&#243;tido y la respuesta al tratamiento con corticoides&#44; la presi&#243;n arterial y los niveles de colesterol en estos pacientes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o y muestra de estudio</span><p id="par0020" class="elsevierStylePara elsevierViewall">Estudio de casos y controles desarrollado en el Hospital Infantil Universitario de El Mansura&#44; Egipto&#44; entre diciembre de 2015 y enero de 2018&#46; La muestra incluy&#243; a 100 ni&#241;os con SN primario &#40;50 con SN corticosensible &#91;SNCS&#93; y 50 con SN corticorresistente &#91;SNCR&#93;&#41;&#44; y a 100 controles sanos&#46; Los controles sanos se seleccionaron en el mismo hospital de entre los pacientes que presentaron problemas menores&#44; como faringitis o gastroenteritis leve&#44; normotensos&#44; an&#225;lisis de orina y pruebas de funci&#243;n renal normales y sin antecedentes de enfermedad renal&#46; Todos los participantes pertenec&#237;an al mismo grupo &#233;tnico&#46; El estudio fue aprobado por el Comit&#233; de Revisi&#243;n Institucional de la Facultad de Medicina de la Universidad de El Mansura&#44; Egipto &#40;N&#250;mero&#58; MS&#47;15&#46;09&#46;47&#41; y se llev&#243; a cabo de acuerdo con los principios &#233;ticos de la Declaraci&#243;n de Helsinki de 1964 y enmiendas posteriores&#46; Se obtuvo el consentimiento informado por escrito de los responsables legales de los casos y los controles&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Evaluaci&#243;n cl&#237;nica y pruebas de laboratorio</span><p id="par0025" class="elsevierStylePara elsevierViewall">En todos los pacientes se realiz&#243; evaluaci&#243;n cl&#237;nica y se recogieron muestras de sangre y orina para determinaci&#243;n de alb&#250;mina&#44; colesterol&#44; creatinina y urea plasm&#225;ticas y proteinuria en muestra de 24&#160;h&#46; Todos los casos presentaron edema generalizado&#44; alb&#250;mina plasm&#225;tica<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#44;5<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; proteinuria &#8805;<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> por hora e hiperlipidemia<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a>&#46; Todos los participantes ten&#237;an un &#237;ndice de masa corporal &#40;IMC&#41; entre los percentiles 10 y 75&#44; y se tuvo en consideraci&#243;n que podr&#237;a existir una interacci&#243;n entre las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y el IMC<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">16</span></a>&#46; Se calcul&#243; el valor de la presi&#243;n arterial obteniendo la media de 3 mediciones y se clasific&#243; como normal hallarse por debajo del percentil 90&#44; como prehipertensi&#243;n en caso de hallarse entre los percentiles 90 y 95 y como hipertensi&#243;n hallarse por encima del percentil 95 para la edad&#44; el sexo y la talla<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a>&#46; Los datos sobre la histopatolog&#237;a renal se recogieron de las historias cl&#237;nicas de los pacientes &#40;65 casos&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">El SNCS se defini&#243; como remisi&#243;n completa a las 4 semanas de tratamiento con prednisona a una dosis de 60<span class="elsevierStyleHsp" style=""></span>mg&#47;m<span class="elsevierStyleSup">2</span> al d&#237;a y el SNCR como la falta de remisi&#243;n completa tras 4 semanas de dicho tratamiento&#46; Se consider&#243; que los pacientes se encontraban en remisi&#243;n si no se detect&#243; alb&#250;mina o si hab&#237;a solo trazas en 3 muestras consecutivas de la primera orina de la ma&#241;ana<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a>&#46; Se excluy&#243; a pacientes con SN cong&#233;nito o secundario&#44; enfermedad renal poliqu&#237;stica&#44; obesidad o diabetes mellitus&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Genotipado de las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span></span><p id="par0035" class="elsevierStylePara elsevierViewall">Se recogieron 3<span class="elsevierStyleHsp" style=""></span>ml de sangre venosa por participante&#44; con jeringuillas de pl&#225;stico y t&#233;cnica as&#233;ptica&#46; El ADN gen&#243;mico se extrajo de muestras de sangre total de 200<span class="elsevierStyleHsp" style=""></span>&#956;L mediante adsorci&#243;n en columnas &#40;Generation DNA Purification capture column kits&#44; Fermentas&#44; EE&#46;&#160;UU&#46;&#41;&#46; La detecci&#243;n de las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> se realiz&#243; mediante reacci&#243;n en cadena de la polimerasa &#40;PCR&#41; con amplificaci&#243;n de alelos espec&#237;ficos &#40;sistema de mutaci&#243;n refractario a la amplificaci&#243;n por PCR&#44; o PCR-ARMS&#41;&#44; emple&#225;ndose los siguientes cebadores<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a>&#58;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Cebador gen&#233;rico reverso&#58; 5&#8242;-AGTCAGGAACCAGCAGAGGA-3&#8242;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Cebador espec&#237;fico de alelo G&#58; 5&#8242;-ATCCGAAGCTGAAAGGCAAG-3&#8242;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Cebador espec&#237;fico de alelo T&#58; 5&#8242;-ATCCGAAGCTGAAAGGCAAT-3&#8242;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Las mezclas para la PCR se prepararon en 2 tubos Eppendorf&#46; A cada tubo se a&#241;adieron 3<span class="elsevierStyleHsp" style=""></span>&#956;L de ADN&#44; 10<span class="elsevierStyleHsp" style=""></span>&#956;l de mezcla maestra Green PCR Master Mix &#40;Fermentas&#41; y 4<span class="elsevierStyleHsp" style=""></span>&#956;l de cebador gen&#233;rico &#40;10<span class="elsevierStyleHsp" style=""></span>pmol&#47;&#956;l&#41;&#46; A continuaci&#243;n&#44; se a&#241;adieron 3<span class="elsevierStyleHsp" style=""></span>&#956;l de cebador espec&#237;fico &#40;alelo G o T&#44; 10<span class="elsevierStyleHsp" style=""></span>pmol&#47;&#956;l&#41;&#46; La secuencia del proceso de PCR comenz&#243; con un paso de desnaturalizaci&#243;n a 95<span class="elsevierStyleHsp" style=""></span>&#176;C durante 5&#160;min&#44; seguido de 35 ciclos a 95<span class="elsevierStyleHsp" style=""></span>&#176;C durante 60 s&#44; 58<span class="elsevierStyleHsp" style=""></span>&#176;C durante 45 s y 72<span class="elsevierStyleHsp" style=""></span>&#176;C durante 45 s&#44; y un &#250;ltimo paso de extensi&#243;n a 72<span class="elsevierStyleHsp" style=""></span>&#176;C durante 5&#160;min&#46; Terminada la reacci&#243;n&#44; se aplic&#243; una temperatura de conservaci&#243;n de 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Los productos de la PCR fueron sometidos a electroforesis en gel de agarosa al 2&#44;5&#37;&#46; Por &#250;ltimo&#44; se visualizaron los productos de la PCR con luz ultravioleta y bromuro de etidio&#46; Se detectaron fragmentos del gen <span class="elsevierStyleItalic">EDN1</span> correspondientes a variantes del polimorfismo rs5370 de 184 pares de bases &#40;pb&#41;&#44; que se fotografiaron con una c&#225;mara digital&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Se clasific&#243; a los pacientes como genotipo GT si se detectaban 2<span class="elsevierStyleHsp" style=""></span>bandas a la altura de 184&#160;pb&#44; una en la calle correspondiente al cebador del alelo T y otra en la calle del cebador de alelo G&#46; Se clasific&#243; a los pacientes como genotipo TT de visualizarse una sola banda a la altura de 184&#160;pb en la calle del cebador T sin ninguna banda en la calle correspondiente al cebador G&#46; Se clasific&#243; a los pacientes como genotipo GG de visualizarse una sola banda a la altura de 184&#160;pb en la calle del cebador G sin ninguna banda en la calle correspondiente al cebador T &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 y 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">An&#225;lisis estad&#237;stico</span><p id="par0065" class="elsevierStylePara elsevierViewall">Para el an&#225;lisis estad&#237;stico se utiliz&#243; el paquete SPSS versi&#243;n 23&#46; Se utiliz&#243; la prueba &#967;<span class="elsevierStyleSup">2</span> para analizar el equilibrio Hardy-Weinberg en la distribuci&#243;n de los genotipos y las frecuencias al&#233;licas del locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#707;<span class="elsevierStyleHsp" style=""></span>0&#44;05 en todos los grupos&#41;&#46; Las variables categ&#243;ricas &#40;expresadas como frecuencias absolutas y porcentajes&#41; se compararon mediante la prueba exacta de Fisher y la prueba &#967;<span class="elsevierStyleSup">2</span>&#46; Para el an&#225;lisis de normalidad de los datos continuos se utiliz&#243; la prueba de Kolmogorov-Smirnov&#46; Las variables no param&#233;tricas se han resumido como mediana y rango &#40;m&#237;nimo-m&#225;ximo&#41; y comparado por medio de la prueba de Kruskal-Wallis&#46; La significaci&#243;n estad&#237;stica se estableci&#243; en <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0070" class="elsevierStylePara elsevierViewall">Los pacientes en los distintos grupos se parearon por edad&#44; sexo&#44; &#225;mbito de residencia &#40;urbano&#47;rural&#41;&#44; percentil del IMC y valores de presi&#243;n arterial &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; La distribuci&#243;n de los genotipos en el locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> fue&#58; GG 18&#37;&#44; GT 70&#37; y TT 12&#37; en el grupo de SN&#44; y GG 7&#37;&#44; GT 88&#37; y TT 5&#37; en el grupo de control&#46; Se observ&#243; que el genotipo GT fue el m&#225;s frecuente en el grupo de control &#40;88&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; mientras que el GG fue m&#225;s frecuente en el grupo de SN que en el grupo de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">El an&#225;lisis de la frecuencia de los alelos G y T en el locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> no mostr&#243; diferencias significativas entre los pacientes con SN y los controles &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;69&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; El an&#225;lisis de regresi&#243;n log&#237;stica binaria revel&#243; que el genotipo GG se asocia a un riesgo 3&#44;23 veces mayor de desarrollar SN que el genotipo GT &#40;<span class="elsevierStyleItalic">odds ratio</span>&#58; 3&#44;23&#59; intervalo de confianza del 95&#37;&#58; 1&#44;28-8&#44;2&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">En cuanto a la respuesta al tratamiento con corticoides&#44; observamos que el genotipo GG era m&#225;s prevalente en el grupo de SNCS que en los grupos de SNCR y de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#41;&#46; No se encontraron diferencias significativas en la distribuci&#243;n de frecuencias al&#233;licas entre los grupos de control&#44; de SNCS y de SNCR &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;89&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">El genotipo GT se asoci&#243; a una presi&#243;n arterial normal en ni&#241;os con SN &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#44; mientras que el genotipo GG se asoci&#243; a la hipertensi&#243;n arterial &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; No se observaron diferencias significativas en los niveles de colesterol en sangre entre los subgrupos de pacientes con SN respecto a los genotipos estudiados &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;068&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">En cuanto a la histopatolog&#237;a renal &#40;datos disponibles en 65&#47;100 casos&#41;&#44; no se encontraron diferencias significativas respecto al genotipo del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discusi&#243;n</span><p id="par0095" class="elsevierStylePara elsevierViewall">El SN primario es una nefropat&#237;a com&#250;n en la edad pedi&#225;trica&#46; Aunque se han publicado varios estudios centrados en el gen <span class="elsevierStyleItalic">EDN1</span> como posible locus de susceptibilidad a la enfermedad renal cr&#243;nica en ni&#241;os&#44; se desconoce su papel exacto en el SN<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a>&#46; Se realiz&#243; un estudio preliminar para evaluar el impacto del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN primario&#46; El genotipo GG del locus rs5370 era m&#225;s prevalente en ni&#241;os con SN que en los controles y se asoci&#243; a un riesgo 3&#44;23 veces mayor de SN&#46; Esto indica que el genotipo GG podr&#237;a desempe&#241;ar un papel importante en la patogenia del SN primario&#46; Las mutaciones en el locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> pueden dar lugar a una sustituci&#243;n lisina&#8594;asparagina en el cod&#243;n 198 &#40;K198N&#41;&#44; lo que resultar&#237;a en la inducci&#243;n de la conversi&#243;n de la preproendotelina&#44; que afectar&#237;a a la s&#237;ntesis de la ET-1<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a> y finalmente producir&#237;a cambios estructurales en los podocitos<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">21-23</span></a>&#46; No obstante&#44; esta hip&#243;tesis a&#250;n ha de confirmarse mediante el an&#225;lisis de la correlaci&#243;n entre las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y los niveles de ET-1 en estudios futuros&#46; Tambi&#233;n son necesarios estudios del ARNm del <span class="elsevierStyleItalic">EDN1</span> para demostrar el impacto funcional de las variantes del polimorfismo rs5370&#46; Los resultados encontrados en la revisi&#243;n bibliogr&#225;fica fueron contradictorios&#46; En China&#44; Yang et al<span class="elsevierStyleItalic">&#46;</span> reportaron una tendencia hacia la diferencia en los genotipos del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> entre 36 ni&#241;os con SN primario y 94 controles &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;057&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a>&#46; Sin embargo&#44; un estudio m&#225;s reciente realizado en Ir&#225;n en 138 ni&#241;os con SN y 150 controles no objetiv&#243; asociaci&#243;n entre las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y el SN<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Las diferencias entre etnias y el tama&#241;o muestral pueden afectar significativamente los resultados de los estudios&#44; lo que subraya la necesidad de abordar estudios multic&#233;ntricos m&#225;s amplios para elucidar el posible papel de los cambios en la secuencia del locus rs5370 en la patogenia del SN primario&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En el presente estudio se observaron diferencias significativas en la frecuencia de los genotipos GG y GT del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> entre los grupos de SNCS&#44; de SNCR y de control&#46; Esto indica una posible implicaci&#243;n de las variantes del polimorfismo rs5370 en la respuesta al tratamiento con corticoides en pacientes con SN&#46; Esto es consistente con los hallazgos de Ezzat et al&#46;&#44; quienes reportaron que la ET-1 y sus receptores est&#225;n implicados en el efecto del tratamiento con glucocorticoides en distintos tipos de c&#233;lulas humanas&#44; incluyendo las del glom&#233;rulo renal<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a>&#46; Tambi&#233;n es consistente con los hallazgos de Ahmed et al&#46;&#44; cuyo estudio mostr&#243; una asociaci&#243;n entre niveles altos de ET-1 en sangre y una mala respuesta a los corticoides en ni&#241;os con SN primario<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Nuestro estudio tambi&#233;n se&#241;ala una posible asociaci&#243;n entre el genotipo GG y la hipertensi&#243;n&#44; mientras que el genotipo GT ser&#237;a m&#225;s prevalente en ni&#241;os con SN y normotensos&#46; Es sabido que la ET-1 es un vasoconstrictor potente que puede afectar a la presi&#243;n arterial<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a>&#46; Los hallazgos de un estudio realizado por Funalot et al&#46; no demostraron una asociaci&#243;n entre el genotipo del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la presi&#243;n arterial&#44; pero indicaban que la interacci&#243;n entre este polimorfismo y los genes que codifican la enzima convertidora de ET-1 pueden modular la presi&#243;n arterial en mujeres<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a>&#46; Wiltshire et al<span class="elsevierStyleItalic">&#46;</span> estudiaron variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en 1&#46;109 sujetos en el oeste de Australia y no encontraron una asociaci&#243;n significativa entre dichas variantes y la hipertensi&#243;n arterial &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;27&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a>&#46; No obstante&#44; hay que tener presente que la patogenia de la hipertensi&#243;n en el SN es multifactorial<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> y que son necesarios estudios adicionales m&#225;s amplios que incluyan m&#225;s variables en el an&#225;lisis para establecer la asociaci&#243;n entre el polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la hipertensi&#243;n en ni&#241;os con SN primario&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">En nuestro estudio no se observ&#243; una asociaci&#243;n significativa entre los genotipos del rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y los niveles plasm&#225;ticos de colesterol&#44; lo que concuerda con los hallazgos de Wiltshire et al<span class="elsevierStyleItalic">&#46;</span> y Hashemi et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">10&#44;24</span></a>&#44; aunque diverge de los de Pare et al<span class="elsevierStyleItalic">&#46;</span> y Yang et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">11&#44;14</span></a><span class="elsevierStyleItalic">&#46;</span> Tampoco se observ&#243; asociaci&#243;n entre el genotipo del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la histopatolog&#237;a renal&#46; Esta posible asociaci&#243;n no se ha explorado en la bibliograf&#237;a publicada hasta la fecha&#44; y se requieren m&#225;s datos para confirmar nuestros resultados&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusi&#243;n</span><p id="par0120" class="elsevierStylePara elsevierViewall">El genotipo GG en el polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> se asoci&#243; a un riesgo mayor de SN primario en la infancia y a una respuesta m&#225;s favorable a los corticoides&#46; Se requieren estudios multic&#233;ntricos de mayor tama&#241;o para validar los hallazgos del presente estudio&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Limitaciones del estudio</span><p id="par0125" class="elsevierStylePara elsevierViewall">Estudio unic&#233;ntrico en muestra peque&#241;a&#46; No se analiz&#243; la asociaci&#243;n con los niveles s&#233;ricos de ET-1&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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              "titulo" => "Genotipado de las variantes del polimorfismo rs5370 del gen EDN1"
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    "fechaRecibido" => "2019-11-25"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El s&#237;ndrome nefr&#243;tico &#40;SN&#41; primario es una glomerulopat&#237;a com&#250;n en la edad pedi&#225;trica&#46; Se evaluaron los genotipos y frecuencias al&#233;licas del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN primario&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio de casos y controles realizado en el Hospital Infantil Universitario de El Mansura&#44; Egipto&#44; de diciembre de 2015 a enero de 2018&#46; Se seleccion&#243; a 50 pacientes con SN corticosensible &#40;SNCS&#41; y a 50 con SN corticorresistente &#40;SNCR&#41;&#44; as&#237; como a 100 controles sanos&#46; Adem&#225;s de una evaluaci&#243;n cl&#237;nica de los pacientes&#44; se hicieron pruebas de cuantificaci&#243;n de alb&#250;mina&#44; colesterol&#44; creatinina y urea s&#233;ricas y de proteinuria en muestra de orina de 24&#160;h&#46; Se emplearon t&#233;cnicas de reacci&#243;n en cadena de la polimerasa para analizar los genotipos &#40;GG&#44; GT y TT&#41; y los alelos &#40;T y G&#41; del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en los grupos en estudio&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El genotipo GT fue el m&#225;s frecuente del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en el grupo de control &#40;88&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; mientras que el genotipo GG fue m&#225;s frecuente en el grupo con SN que en el de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41;&#46; No se encontraron diferencias estad&#237;sticamente significativas entre los grupos de SN y de control en los alelos del polimorfismo rs5370 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;69&#41;&#46; El genotipo GG fue m&#225;s prevalente en el grupo de SNSC que en los grupos de SNRC y de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#41;&#46; Las diferencias en las frecuencias al&#233;licas entre los grupos de SNRC&#44; SNSC y de control no fueron significativas &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;89&#41;&#46; El genotipo GT se asoci&#243; a una presi&#243;n arterial normal en ni&#241;os con SN &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; mientras que el genotipo GG se asoci&#243; a hipertensi&#243;n &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; No se detectaron diferencias significativas en la histopatolog&#237;a renal ni en los niveles s&#233;ricos de colesterol respecto al genotipo&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El genotipo GG del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> podr&#237;a asociarse a un riesgo mayor de desarrollar SN y a una respuesta m&#225;s favorable al tratamiento con corticoides&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Primary nephrotic syndrome &#40;NS&#41; is a common glomerular disease in children&#46; We assessed the genotypes and frequency of the rs5370 allelic variant of the <span class="elsevierStyleItalic">EDN1</span> gene in children with primary NS&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We conducted a case-control study in Mansoura University Children&#39;s Hospital&#44; Egypt&#44; between December 2015 and January 2018&#46; We recruited 50 patients with steroid-sensitive NS &#40;SSNS&#41; and 50 patients with steroid-resistant NS &#40;SRNS&#41; in addition to 100 healthy controls&#46; The patients underwent clinical evaluations and tests including measurement of serum albumin&#44; cholesterol&#44; creatinine and urea levels and a 24-hour urinary protein test&#46; We used polymerase chain reaction methods to assess the genotypes of rs5370 variants of the <span class="elsevierStyleItalic">EDN1</span> gene &#40;GG&#44; GT and TT&#41; and alleles &#40;T and G&#41; in the groups under study&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The most frequent genotype of the <span class="elsevierStyleItalic">EDN1</span> gene at the locus of interest in the control group was the GT genotype &#40;88&#37;&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; while the GG genotype was more frequent in the NS group compared to the control group &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;02&#41;&#46; We did not find statistically significant differences between the NS and control groups in regard to the <span class="elsevierStyleItalic">EDN1</span> rs5370 alleles &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;69&#41;&#46; The GG genotype was more frequent in the SSNS group compared to the SRNS and control groups &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;03&#41;&#46; When we compared allele frequencies between the control&#44; SSNS and SRNS groups&#44; we did not find significant differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;89&#41;&#46; The GT genotype was associated with normal blood pressure in children with NS &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#44; while the GG genotype was associated with hypertension &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; We did not find statistically significant differences in renal histopathology or serum cholesterol levels based on the genotype&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The GG genotype at the rs5370 locus of the <span class="elsevierStyleItalic">EDN1</span> gene may be associated with an increased risk of primary NS and a better response to steroid therapy&#46;</p></span>"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Productos de la amplificaci&#243;n del locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> mediante reacci&#243;n en cadena de la polimerasa &#40;PCR-ARMS&#41; con identificaci&#243;n de los genotipos GT &#40;calles 1-6&#44; 9-12&#41; y TT &#40;calles 7&#44; 8&#41;&#59; la calle M corresponde al marcador de peso molecular&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">L&#58; calle&#46;</p>"
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Productos de la amplificaci&#243;n del locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> mediante reacci&#243;n en cadena de la polimerasa &#40;PCR-ARMS&#41; con identificaci&#243;n de los genotipos GT &#40;calles 3-6&#44; 9&#44; 10&#41; y GG &#40;calles 1&#44; 2&#44; 7&#44; 8&#41;&#59; la calle M corresponde al marcador de peso molecular&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">L&#58; calle&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;sticas cl&#237;nicas&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Edad en a&#241;os</span> mediana &#40;rango&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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          "es" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas cl&#237;nicas de los ni&#241;os con s&#237;ndrome nefr&#243;tico primario y los controles</p>"
        ]
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            "identificador" => "at2"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">EDN1&#58;</span> gen de la endotelina-1&#59; SN&#58; s&#237;ndrome nefr&#243;tico&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>GT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="" valign="\n
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            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Distribuci&#243;n de los genotipos y los aleles del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con s&#237;ndrome nefr&#243;tico primario y controles</p>"
        ]
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                  \t\t\t\t  " align="left" valign="\n
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    "bibliografia" => array:2 [
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          "identificador" => "bibs0015"
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                    0 => array:2 [
                      "titulo" => "Nephrotic syndrome in childhood"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46;A&#46; Eddy"
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                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(03)14184-0"
                      "Revista" => array:6 [
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ORIGINAL
Polimorfismo rs5370 del gen de la endotelina-1 en el síndrome nefrótico primario: estudio de casos y controles
Endothelin-1 rs5370 gene polymorphism in primary nephrotic syndrome: A case-control study
Hoda Rizka, Ayman Hammada, Afaf El-Saidb, Yahya Wahbaa,
Autor para correspondencia
a Departamento de Pediatría, Facultad de Medicina, Universidad de El Mansura, El Mansura, Egipto
b Sección de Bioquímica, Hospital Infantil Universitario de El Mansura, El Mansura, Egipto
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">El s&#237;ndrome nefr&#243;tico &#40;SN&#41; primario es una glomerulopat&#237;a com&#250;n en la edad pedi&#225;trica caracterizada por edema generalizado&#44; proteinuria elevada&#44; hipoalbuminemia e hiperlipidemia&#44; con una incidencia estimada de 2-7 casos por cada 100&#46;000 ni&#241;os<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">La endotelina-1 &#40;ET-1&#41; es un p&#233;ptido compuesto de 21 amino&#225;cidos con acci&#243;n promotora del crecimiento y un potente efecto vasoconstrictor<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> codificada por el gen <span class="elsevierStyleItalic">EDN1</span> &#40;6p24&#46;1&#41;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; Hay datos convincentes de que la ET-1 desempe&#241;a un papel importante en la patogenia de la proteinuria y la glomeruloesclerosis mediante la activaci&#243;n del receptor de la ET-1 tipo A&#44; que produce estr&#233;s oxidativo y da&#241;a las c&#233;lulas endoteliales adyacentes del glom&#233;rulo renal mediante un mecanismo paracrino que tambi&#233;n causa un da&#241;o rec&#237;proco a los podocitos<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Varios estudios han analizado la asociaci&#243;n entre el polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la hipertensi&#243;n&#44; la presi&#243;n arterial sist&#243;lica y el nivel de colesterol de las lipoprote&#237;nas de alta densidad&#44; aunque con resultados contradictorios<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">6-11</span></a>&#46; Con relaci&#243;n a las nefropat&#237;as&#44; las variantes del gen <span class="elsevierStyleItalic">EDN1</span> se han asociado con la progresi&#243;n de la enfermedad renal poliqu&#237;stica autos&#243;mica dominante<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> y la nefropat&#237;a IgA<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a>&#46; Los estudios que analizan el impacto de los polimorfismos del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN son escasos<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a>&#46; El objetivo principal de nuestro estudio fue establecer los genotipos y frecuencias al&#233;licas del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN primario&#46; Tambi&#233;n se analiz&#243; la asociaci&#243;n entre las variantes de este polimorfismo de un solo nucle&#243;tido y la respuesta al tratamiento con corticoides&#44; la presi&#243;n arterial y los niveles de colesterol en estos pacientes&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o y muestra de estudio</span><p id="par0020" class="elsevierStylePara elsevierViewall">Estudio de casos y controles desarrollado en el Hospital Infantil Universitario de El Mansura&#44; Egipto&#44; entre diciembre de 2015 y enero de 2018&#46; La muestra incluy&#243; a 100 ni&#241;os con SN primario &#40;50 con SN corticosensible &#91;SNCS&#93; y 50 con SN corticorresistente &#91;SNCR&#93;&#41;&#44; y a 100 controles sanos&#46; Los controles sanos se seleccionaron en el mismo hospital de entre los pacientes que presentaron problemas menores&#44; como faringitis o gastroenteritis leve&#44; normotensos&#44; an&#225;lisis de orina y pruebas de funci&#243;n renal normales y sin antecedentes de enfermedad renal&#46; Todos los participantes pertenec&#237;an al mismo grupo &#233;tnico&#46; El estudio fue aprobado por el Comit&#233; de Revisi&#243;n Institucional de la Facultad de Medicina de la Universidad de El Mansura&#44; Egipto &#40;N&#250;mero&#58; MS&#47;15&#46;09&#46;47&#41; y se llev&#243; a cabo de acuerdo con los principios &#233;ticos de la Declaraci&#243;n de Helsinki de 1964 y enmiendas posteriores&#46; Se obtuvo el consentimiento informado por escrito de los responsables legales de los casos y los controles&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Evaluaci&#243;n cl&#237;nica y pruebas de laboratorio</span><p id="par0025" class="elsevierStylePara elsevierViewall">En todos los pacientes se realiz&#243; evaluaci&#243;n cl&#237;nica y se recogieron muestras de sangre y orina para determinaci&#243;n de alb&#250;mina&#44; colesterol&#44; creatinina y urea plasm&#225;ticas y proteinuria en muestra de 24&#160;h&#46; 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y 4<span class="elsevierStyleHsp" style=""></span>&#956;l de cebador gen&#233;rico &#40;10<span class="elsevierStyleHsp" style=""></span>pmol&#47;&#956;l&#41;&#46; A continuaci&#243;n&#44; se a&#241;adieron 3<span class="elsevierStyleHsp" style=""></span>&#956;l de cebador espec&#237;fico &#40;alelo G o T&#44; 10<span class="elsevierStyleHsp" style=""></span>pmol&#47;&#956;l&#41;&#46; La secuencia del proceso de PCR comenz&#243; con un paso de desnaturalizaci&#243;n a 95<span class="elsevierStyleHsp" style=""></span>&#176;C durante 5&#160;min&#44; seguido de 35 ciclos a 95<span class="elsevierStyleHsp" style=""></span>&#176;C durante 60 s&#44; 58<span class="elsevierStyleHsp" style=""></span>&#176;C durante 45 s y 72<span class="elsevierStyleHsp" style=""></span>&#176;C durante 45 s&#44; y un &#250;ltimo paso de extensi&#243;n a 72<span class="elsevierStyleHsp" style=""></span>&#176;C durante 5&#160;min&#46; Terminada la reacci&#243;n&#44; se aplic&#243; una temperatura de conservaci&#243;n de 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Los productos de la PCR fueron sometidos a electroforesis en gel de agarosa al 2&#44;5&#37;&#46; Por &#250;ltimo&#44; se visualizaron los productos de la PCR con luz ultravioleta y bromuro de etidio&#46; Se detectaron fragmentos del gen <span class="elsevierStyleItalic">EDN1</span> correspondientes a variantes del polimorfismo rs5370 de 184 pares de bases &#40;pb&#41;&#44; que se fotografiaron con una c&#225;mara digital&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Se clasific&#243; a los pacientes como genotipo GT si se detectaban 2<span class="elsevierStyleHsp" style=""></span>bandas a la altura de 184&#160;pb&#44; una en la calle correspondiente al cebador del alelo T y otra en la calle del cebador de alelo G&#46; Se clasific&#243; a los pacientes como genotipo TT de visualizarse una sola banda a la altura de 184&#160;pb en la calle del cebador T sin ninguna banda en la calle correspondiente al cebador G&#46; Se clasific&#243; a los pacientes como genotipo GG de visualizarse una sola banda a la altura de 184&#160;pb en la calle del cebador G sin ninguna banda en la calle correspondiente al cebador T &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 y 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">An&#225;lisis estad&#237;stico</span><p id="par0065" class="elsevierStylePara elsevierViewall">Para el an&#225;lisis estad&#237;stico se utiliz&#243; el paquete SPSS versi&#243;n 23&#46; Se utiliz&#243; la prueba &#967;<span class="elsevierStyleSup">2</span> para analizar el equilibrio Hardy-Weinberg en la distribuci&#243;n de los genotipos y las frecuencias al&#233;licas del locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#707;<span class="elsevierStyleHsp" style=""></span>0&#44;05 en todos los grupos&#41;&#46; Las variables categ&#243;ricas &#40;expresadas como frecuencias absolutas y porcentajes&#41; se compararon mediante la prueba exacta de Fisher y la prueba &#967;<span class="elsevierStyleSup">2</span>&#46; Para el an&#225;lisis de normalidad de los datos continuos se utiliz&#243; la prueba de Kolmogorov-Smirnov&#46; Las variables no param&#233;tricas se han resumido como mediana y rango &#40;m&#237;nimo-m&#225;ximo&#41; y comparado por medio de la prueba de Kruskal-Wallis&#46; La significaci&#243;n estad&#237;stica se estableci&#243; en <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Resultados</span><p id="par0070" class="elsevierStylePara elsevierViewall">Los pacientes en los distintos grupos se parearon por edad&#44; sexo&#44; &#225;mbito de residencia &#40;urbano&#47;rural&#41;&#44; percentil del IMC y valores de presi&#243;n arterial &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46; La distribuci&#243;n de los genotipos en el locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> fue&#58; GG 18&#37;&#44; GT 70&#37; y TT 12&#37; en el grupo de SN&#44; y GG 7&#37;&#44; GT 88&#37; y TT 5&#37; en el grupo de control&#46; Se observ&#243; que el genotipo GT fue el m&#225;s frecuente en el grupo de control &#40;88&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; mientras que el GG fue m&#225;s frecuente en el grupo de SN que en el grupo de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">El an&#225;lisis de la frecuencia de los alelos G y T en el locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> no mostr&#243; diferencias significativas entre los pacientes con SN y los controles &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;69&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#41;&#46; El an&#225;lisis de regresi&#243;n log&#237;stica binaria revel&#243; que el genotipo GG se asocia a un riesgo 3&#44;23 veces mayor de desarrollar SN que el genotipo GT &#40;<span class="elsevierStyleItalic">odds ratio</span>&#58; 3&#44;23&#59; intervalo de confianza del 95&#37;&#58; 1&#44;28-8&#44;2&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">En cuanto a la respuesta al tratamiento con corticoides&#44; observamos que el genotipo GG era m&#225;s prevalente en el grupo de SNCS que en los grupos de SNCR y de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#41;&#46; No se encontraron diferencias significativas en la distribuci&#243;n de frecuencias al&#233;licas entre los grupos de control&#44; de SNCS y de SNCR &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;89&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">El genotipo GT se asoci&#243; a una presi&#243;n arterial normal en ni&#241;os con SN &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41;&#44; mientras que el genotipo GG se asoci&#243; a la hipertensi&#243;n arterial &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; No se observaron diferencias significativas en los niveles de colesterol en sangre entre los subgrupos de pacientes con SN respecto a los genotipos estudiados &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;068&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">En cuanto a la histopatolog&#237;a renal &#40;datos disponibles en 65&#47;100 casos&#41;&#44; no se encontraron diferencias significativas respecto al genotipo del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discusi&#243;n</span><p id="par0095" class="elsevierStylePara elsevierViewall">El SN primario es una nefropat&#237;a com&#250;n en la edad pedi&#225;trica&#46; Aunque se han publicado varios estudios centrados en el gen <span class="elsevierStyleItalic">EDN1</span> como posible locus de susceptibilidad a la enfermedad renal cr&#243;nica en ni&#241;os&#44; se desconoce su papel exacto en el SN<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a>&#46; Se realiz&#243; un estudio preliminar para evaluar el impacto del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN primario&#46; El genotipo GG del locus rs5370 era m&#225;s prevalente en ni&#241;os con SN que en los controles y se asoci&#243; a un riesgo 3&#44;23 veces mayor de SN&#46; Esto indica que el genotipo GG podr&#237;a desempe&#241;ar un papel importante en la patogenia del SN primario&#46; Las mutaciones en el locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> pueden dar lugar a una sustituci&#243;n lisina&#8594;asparagina en el cod&#243;n 198 &#40;K198N&#41;&#44; lo que resultar&#237;a en la inducci&#243;n de la conversi&#243;n de la preproendotelina&#44; que afectar&#237;a a la s&#237;ntesis de la ET-1<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">20</span></a> y finalmente producir&#237;a cambios estructurales en los podocitos<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">21-23</span></a>&#46; No obstante&#44; esta hip&#243;tesis a&#250;n ha de confirmarse mediante el an&#225;lisis de la correlaci&#243;n entre las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y los niveles de ET-1 en estudios futuros&#46; Tambi&#233;n son necesarios estudios del ARNm del <span class="elsevierStyleItalic">EDN1</span> para demostrar el impacto funcional de las variantes del polimorfismo rs5370&#46; Los resultados encontrados en la revisi&#243;n bibliogr&#225;fica fueron contradictorios&#46; En China&#44; Yang et al<span class="elsevierStyleItalic">&#46;</span> reportaron una tendencia hacia la diferencia en los genotipos del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> entre 36 ni&#241;os con SN primario y 94 controles &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;057&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a>&#46; Sin embargo&#44; un estudio m&#225;s reciente realizado en Ir&#225;n en 138 ni&#241;os con SN y 150 controles no objetiv&#243; asociaci&#243;n entre las variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y el SN<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">24</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Las diferencias entre etnias y el tama&#241;o muestral pueden afectar significativamente los resultados de los estudios&#44; lo que subraya la necesidad de abordar estudios multic&#233;ntricos m&#225;s amplios para elucidar el posible papel de los cambios en la secuencia del locus rs5370 en la patogenia del SN primario&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">En el presente estudio se observaron diferencias significativas en la frecuencia de los genotipos GG y GT del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> entre los grupos de SNCS&#44; de SNCR y de control&#46; Esto indica una posible implicaci&#243;n de las variantes del polimorfismo rs5370 en la respuesta al tratamiento con corticoides en pacientes con SN&#46; Esto es consistente con los hallazgos de Ezzat et al&#46;&#44; quienes reportaron que la ET-1 y sus receptores est&#225;n implicados en el efecto del tratamiento con glucocorticoides en distintos tipos de c&#233;lulas humanas&#44; incluyendo las del glom&#233;rulo renal<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a>&#46; Tambi&#233;n es consistente con los hallazgos de Ahmed et al&#46;&#44; cuyo estudio mostr&#243; una asociaci&#243;n entre niveles altos de ET-1 en sangre y una mala respuesta a los corticoides en ni&#241;os con SN primario<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Nuestro estudio tambi&#233;n se&#241;ala una posible asociaci&#243;n entre el genotipo GG y la hipertensi&#243;n&#44; mientras que el genotipo GT ser&#237;a m&#225;s prevalente en ni&#241;os con SN y normotensos&#46; Es sabido que la ET-1 es un vasoconstrictor potente que puede afectar a la presi&#243;n arterial<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a>&#46; Los hallazgos de un estudio realizado por Funalot et al&#46; no demostraron una asociaci&#243;n entre el genotipo del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la presi&#243;n arterial&#44; pero indicaban que la interacci&#243;n entre este polimorfismo y los genes que codifican la enzima convertidora de ET-1 pueden modular la presi&#243;n arterial en mujeres<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a>&#46; Wiltshire et al<span class="elsevierStyleItalic">&#46;</span> estudiaron variantes del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en 1&#46;109 sujetos en el oeste de Australia y no encontraron una asociaci&#243;n significativa entre dichas variantes y la hipertensi&#243;n arterial &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;27&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a>&#46; No obstante&#44; hay que tener presente que la patogenia de la hipertensi&#243;n en el SN es multifactorial<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> y que son necesarios estudios adicionales m&#225;s amplios que incluyan m&#225;s variables en el an&#225;lisis para establecer la asociaci&#243;n entre el polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la hipertensi&#243;n en ni&#241;os con SN primario&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">En nuestro estudio no se observ&#243; una asociaci&#243;n significativa entre los genotipos del rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y los niveles plasm&#225;ticos de colesterol&#44; lo que concuerda con los hallazgos de Wiltshire et al<span class="elsevierStyleItalic">&#46;</span> y Hashemi et al<span class="elsevierStyleItalic">&#46;</span><a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">10&#44;24</span></a>&#44; aunque diverge de los de Pare et al<span class="elsevierStyleItalic">&#46;</span> y Yang et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">11&#44;14</span></a><span class="elsevierStyleItalic">&#46;</span> Tampoco se observ&#243; asociaci&#243;n entre el genotipo del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> y la histopatolog&#237;a renal&#46; Esta posible asociaci&#243;n no se ha explorado en la bibliograf&#237;a publicada hasta la fecha&#44; y se requieren m&#225;s datos para confirmar nuestros resultados&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusi&#243;n</span><p id="par0120" class="elsevierStylePara elsevierViewall">El genotipo GG en el polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> se asoci&#243; a un riesgo mayor de SN primario en la infancia y a una respuesta m&#225;s favorable a los corticoides&#46; Se requieren estudios multic&#233;ntricos de mayor tama&#241;o para validar los hallazgos del presente estudio&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Limitaciones del estudio</span><p id="par0125" class="elsevierStylePara elsevierViewall">Estudio unic&#233;ntrico en muestra peque&#241;a&#46; No se analiz&#243; la asociaci&#243;n con los niveles s&#233;ricos de ET-1&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicto de intereses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introducci&#243;n</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El s&#237;ndrome nefr&#243;tico &#40;SN&#41; primario es una glomerulopat&#237;a com&#250;n en la edad pedi&#225;trica&#46; Se evaluaron los genotipos y frecuencias al&#233;licas del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con SN primario&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio de casos y controles realizado en el Hospital Infantil Universitario de El Mansura&#44; Egipto&#44; de diciembre de 2015 a enero de 2018&#46; Se seleccion&#243; a 50 pacientes con SN corticosensible &#40;SNCS&#41; y a 50 con SN corticorresistente &#40;SNCR&#41;&#44; as&#237; como a 100 controles sanos&#46; Adem&#225;s de una evaluaci&#243;n cl&#237;nica de los pacientes&#44; se hicieron pruebas de cuantificaci&#243;n de alb&#250;mina&#44; colesterol&#44; creatinina y urea s&#233;ricas y de proteinuria en muestra de orina de 24&#160;h&#46; Se emplearon t&#233;cnicas de reacci&#243;n en cadena de la polimerasa para analizar los genotipos &#40;GG&#44; GT y TT&#41; y los alelos &#40;T y G&#41; del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en los grupos en estudio&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El genotipo GT fue el m&#225;s frecuente del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en el grupo de control &#40;88&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; mientras que el genotipo GG fue m&#225;s frecuente en el grupo con SN que en el de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41;&#46; No se encontraron diferencias estad&#237;sticamente significativas entre los grupos de SN y de control en los alelos del polimorfismo rs5370 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;69&#41;&#46; El genotipo GG fue m&#225;s prevalente en el grupo de SNSC que en los grupos de SNRC y de control &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03&#41;&#46; Las diferencias en las frecuencias al&#233;licas entre los grupos de SNRC&#44; SNSC y de control no fueron significativas &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;89&#41;&#46; El genotipo GT se asoci&#243; a una presi&#243;n arterial normal en ni&#241;os con SN &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; mientras que el genotipo GG se asoci&#243; a hipertensi&#243;n &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; No se detectaron diferencias significativas en la histopatolog&#237;a renal ni en los niveles s&#233;ricos de colesterol respecto al genotipo&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El genotipo GG del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> podr&#237;a asociarse a un riesgo mayor de desarrollar SN y a una respuesta m&#225;s favorable al tratamiento con corticoides&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introducci&#243;n"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Pacientes y m&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusiones"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Primary nephrotic syndrome &#40;NS&#41; is a common glomerular disease in children&#46; We assessed the genotypes and frequency of the rs5370 allelic variant of the <span class="elsevierStyleItalic">EDN1</span> gene in children with primary NS&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">We conducted a case-control study in Mansoura University Children&#39;s Hospital&#44; Egypt&#44; between December 2015 and January 2018&#46; We recruited 50 patients with steroid-sensitive NS &#40;SSNS&#41; and 50 patients with steroid-resistant NS &#40;SRNS&#41; in addition to 100 healthy controls&#46; The patients underwent clinical evaluations and tests including measurement of serum albumin&#44; cholesterol&#44; creatinine and urea levels and a 24-hour urinary protein test&#46; We used polymerase chain reaction methods to assess the genotypes of rs5370 variants of the <span class="elsevierStyleItalic">EDN1</span> gene &#40;GG&#44; GT and TT&#41; and alleles &#40;T and G&#41; in the groups under study&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The most frequent genotype of the <span class="elsevierStyleItalic">EDN1</span> gene at the locus of interest in the control group was the GT genotype &#40;88&#37;&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; while the GG genotype was more frequent in the NS group compared to the control group &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;02&#41;&#46; We did not find statistically significant differences between the NS and control groups in regard to the <span class="elsevierStyleItalic">EDN1</span> rs5370 alleles &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;69&#41;&#46; The GG genotype was more frequent in the SSNS group compared to the SRNS and control groups &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;03&#41;&#46; When we compared allele frequencies between the control&#44; SSNS and SRNS groups&#44; we did not find significant differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;89&#41;&#46; The GT genotype was associated with normal blood pressure in children with NS &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;007&#41;&#44; while the GG genotype was associated with hypertension &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; We did not find statistically significant differences in renal histopathology or serum cholesterol levels based on the genotype&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The GG genotype at the rs5370 locus of the <span class="elsevierStyleItalic">EDN1</span> gene may be associated with an increased risk of primary NS and a better response to steroid therapy&#46;</p></span>"
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            "titulo" => "Introduction"
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            "identificador" => "abst0030"
            "titulo" => "Patients and methods"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Results"
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            "identificador" => "abst0040"
            "titulo" => "Conclusions"
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Productos de la amplificaci&#243;n del locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> mediante reacci&#243;n en cadena de la polimerasa &#40;PCR-ARMS&#41; con identificaci&#243;n de los genotipos GT &#40;calles 1-6&#44; 9-12&#41; y TT &#40;calles 7&#44; 8&#41;&#59; la calle M corresponde al marcador de peso molecular&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">L&#58; calle&#46;</p>"
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        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Productos de la amplificaci&#243;n del locus rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> mediante reacci&#243;n en cadena de la polimerasa &#40;PCR-ARMS&#41; con identificaci&#243;n de los genotipos GT &#40;calles 3-6&#44; 9&#44; 10&#41; y GG &#40;calles 1&#44; 2&#44; 7&#44; 8&#41;&#59; la calle M corresponde al marcador de peso molecular&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">L&#58; calle&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Datos expresados como frecuencias absolutas y porcentajes&#44; salvo &#42;mediana &#40;m&#237;nimo-m&#225;ximo&#41;&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">SNCR&#58; s&#237;ndrome nefr&#243;tico corticorresistente&#59; SNCS&#58; s&#237;ndrome nefr&#243;tico corticosensible&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;sticas cl&#237;nicas&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t">12 &#40;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Frecuencia al&#233;lica &#40;2 n&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">106 &#40;53&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2785279.png"
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        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Distribuci&#243;n de los genotipos y los aleles del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con s&#237;ndrome nefr&#243;tico primario y controles</p>"
        ]
      ]
      4 => array:8 [
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        "mostrarFloat" => true
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          ]
        ]
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">EDN1&#58;</span> gen de la endotelina-1&#59; SNCR&#44; s&#237;ndrome nefr&#243;tico corticorresistente&#59; SNCS&#58; s&#237;ndrome nefr&#243;tico corticosensible&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grupo de SNCR &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#41;<span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Grupo de control &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>100&#41;<span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>GG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">7 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">7 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">88 &#40;88&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Frecuencia al&#233;lica &#40;2 n&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;52&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">102 &#40;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98 &#40;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2785275.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Distribuci&#243;n de los genotipos y los aleles del polimorfismo rs5370 del gen <span class="elsevierStyleItalic">EDN1</span> en ni&#241;os con s&#237;ndrome nefr&#243;tico corticosensible&#41;&#44; s&#237;ndrome nefr&#243;tico corticorresistente y controles</p>"
        ]
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      5 => array:8 [
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        "etiqueta" => "Tabla 4"
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        "mostrarFloat" => true
        "mostrarDisplay" => false
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          0 => array:3 [
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          ]
        ]
        "tabla" => array:1 [
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Información del artículo
ISSN: 16954033
Idioma original: Español
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