<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1889-836X</journal-id>
<journal-title><![CDATA[Revista de Osteoporosis y Metabolismo Mineral]]></journal-title>
<abbrev-journal-title><![CDATA[Rev Osteoporos Metab Miner]]></abbrev-journal-title>
<issn>1889-836X</issn>
<publisher>
<publisher-name><![CDATA[Sociedad Española de Investigaciones Óseas y Metabolismo Mineral]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1889-836X2019000400004</article-id>
<article-id pub-id-type="doi">10.4321/s1889-836x2019000400004</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Impacto funcional de polimorfismos del gen de la esclerostina sobre la metilación de ADN y la expresión génica]]></article-title>
<article-title xml:lang="en"><![CDATA[Functional impact of sclerostin gene polymorphisms on DNA methylation and gene expression]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Real]]></surname>
<given-names><![CDATA[A Del]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aa "/>
<xref ref-type="aff" rid="Af0"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sañudo]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aa "/>
<xref ref-type="aff" rid="Af0"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[García-Ibarbia]]></surname>
<given-names><![CDATA[C]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aa "/>
<xref ref-type="aff" rid="Af0"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Santurtún]]></surname>
<given-names><![CDATA[A]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Zarrabeitia]]></surname>
<given-names><![CDATA[MT]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
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<contrib contrib-type="author">
<name>
<surname><![CDATA[Pérez-Núñez]]></surname>
<given-names><![CDATA[MI]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="A a"/>
<xref ref-type="aff" rid="A01"/>
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<contrib contrib-type="author">
<name>
<surname><![CDATA[Laguna]]></surname>
<given-names><![CDATA[E]]></given-names>
</name>
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<xref ref-type="aff" rid="A a"/>
<xref ref-type="aff" rid="A01"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[López-Delgado]]></surname>
<given-names><![CDATA[L]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aa "/>
<xref ref-type="aff" rid="Af0"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Fernández]]></surname>
<given-names><![CDATA[AF]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aa "/>
<xref ref-type="aff" rid="Af0"/>
<xref ref-type="aff" rid="A a"/>
<xref ref-type="aff" rid="A04"/>
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<surname><![CDATA[Fraga]]></surname>
<given-names><![CDATA[MF]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aa "/>
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<xref ref-type="aff" rid="A05"/>
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<surname><![CDATA[Riancho]]></surname>
<given-names><![CDATA[JA]]></given-names>
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<xref ref-type="aff" rid="Aa "/>
<xref ref-type="aff" rid="Af0"/>
</contrib>
</contrib-group>
<aff id="A1a">
<institution><![CDATA[,Hospital Universitario Marqués de Valdecilla Servicio de Medicina Interna ]]></institution>
<addr-line><![CDATA[Santander ]]></addr-line>
<country>España</country>
</aff>
<aff id="A1b">
<institution><![CDATA[,Universidad de Cantabria Instituto de Investigación Sanitaria Valdecilla ]]></institution>
<addr-line><![CDATA[Santander ]]></addr-line>
<country>España</country>
</aff>
<aff id="A02">
<institution><![CDATA[,Universidad de Cantabria Facultad de Medicina Departamento de Medicina Legal]]></institution>
<addr-line><![CDATA[Santander ]]></addr-line>
<country>España</country>
</aff>
<aff id="A03">
<institution><![CDATA[,Hospital Universitario Marqués de Valdecilla Servicio de Traumatología ]]></institution>
<addr-line><![CDATA[Santander ]]></addr-line>
<country>España</country>
</aff>
<aff id="A4a">
<institution><![CDATA[,Instituto Universitario de Oncología del Principado de Asturias  ]]></institution>
<addr-line><![CDATA[ Asturias]]></addr-line>
<country>España</country>
</aff>
<aff id="A4b">
<institution><![CDATA[,Instituto de Investigación Sanitaria del Principado de Asturias  ]]></institution>
<addr-line><![CDATA[ Asturias]]></addr-line>
<country>España</country>
</aff>
<aff id="A4c">
<institution><![CDATA[,Hospital Universitario Central de Asturias  ]]></institution>
<addr-line><![CDATA[ Asturias]]></addr-line>
<country>España</country>
</aff>
<aff id="A4d">
<institution><![CDATA[,Fundación para la Investigación Biosanitaria de Asturias  ]]></institution>
<addr-line><![CDATA[ Asturias]]></addr-line>
<country>España</country>
</aff>
<aff id="A5a">
<institution><![CDATA[,Instituto Universitario de Oncología del Principado de Asturias Laboratorio de Epigenética del Cáncer. ]]></institution>
<addr-line><![CDATA[Oviedo Asturias]]></addr-line>
<country>España</country>
</aff>
<aff id="A5b">
<institution><![CDATA[,Consejo Superior de Investigaciones Científicas Centro de Investigación de Nanomateriales y Nanotecnología ]]></institution>
<addr-line><![CDATA[Oviedo Asturias]]></addr-line>
<country>España</country>
</aff>
<aff id="A5c">
<institution><![CDATA[,Universidad de Oviedo  ]]></institution>
<addr-line><![CDATA[Oviedo Asturias]]></addr-line>
<country>España</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>12</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>12</month>
<year>2019</year>
</pub-date>
<volume>11</volume>
<numero>4</numero>
<fpage>98</fpage>
<lpage>104</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_arttext&amp;pid=S1889-836X2019000400004&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_abstract&amp;pid=S1889-836X2019000400004&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.isciii.es/scielo.php?script=sci_pdf&amp;pid=S1889-836X2019000400004&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen  Introducción: Varios estudios de barrido genómico (GWAS) y otros focalizados en el gen de la esclerostina (SOST) han encontrado que algunos polimorfismos de SOST se asocian con la masa ósea y el riesgo de fracturas. El objetivo de este estudio fue analizar la relevancia funcional de ciertos polimorfismos de la región promotora de SOST, en relación con la expresión y la metilación de dicho gen  Material y método: Para ello, se determinaron los alelos de los polimorfismos rs851054, rs851056, rs10534024, rs1234612 y se analizó la metilación de ADN de 33 muestras de suero y de hueso, procedentes de pacientes intervenidos para colocar una prótesis de cadera, mediante pirosecuenciación tras conversión con bisulfito. Además, en el hueso se estudió la expresión de SOST. Por último, se clonaron diferentes alelos del promotor de SOST en vectores reporteros dobles con el gen de la luciferasa bajo dicho promotor y el gen de la fosfatasa alcalina bajo un promotor constitutivo.  Resultados: El análisis de metilación de la región promotora de SOST en ADN libre en suero y en ADN de hueso no reveló diferencias estadísticamente significativas en relación con los alelos de los polimorfismos analizados (p&gt;0,05). Sin embargo, las transfecciones con los vectores reporteros mostraron una elevada actividad transcripcional, independiente mente del vector utilizado.  Conclusión: No hemos encontrado una asociación clara entre los distintos alelos y la metilación de ADN de la región promotora del gen SOST. Son necesarios más estudios para determinar los efectos funcionales de los polimorfismos sobre la metilación y expresión del gen de SOST y los efectos sobre la masa ósea.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Summary  Introduction: Several genome-wide association studies (GWAS) and others which focused on the sclerostin gene (SOST) have found that some SOST polymorphisms are associated with bone mass and risk of fractures. This study analyzes the functional relevance of certain polymorphisms of the SOST promoter region, and their relationship with the expression and methylation of this gene  Material and method: Alleles of the rs851054, rs851056, rs10534024, rs1234612 polymorphisms and DNA methylation were analyzed by pyrosequencing in serum and bone samples of 33 patients undergoing hip replacement. In addition, SOST expression was studied in bone samples. Also, different alleles of the SOST promoter were cloned into double reporter vectors with the luciferase gene under this promoter and the alkaline phosphatase gene under a constitutive promoter  Results: Methylation analysis of the SOST promoter region in serum free DNA and bone DNA revealed no statistically significant differences across the alleles of the analyzed polymorphisms (p&gt;0.05). However, transfections with reporter vectors showed high transcriptional activity, regardless of the vector used.  Conclusions: We have not found a clear association between the different alleles and the DNA methylation of the SOST promoter region. Further studies are needed to determine the polymorphisms' functional effects on the methylation and expression of the SOST gene and the consequences on bone mass.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[ADN libre en suero]]></kwd>
<kwd lng="es"><![CDATA[metilación de ADN]]></kwd>
<kwd lng="es"><![CDATA[polimorfismos]]></kwd>
<kwd lng="es"><![CDATA[esclerostina]]></kwd>
<kwd lng="es"><![CDATA[osteoporosis]]></kwd>
<kwd lng="es"><![CDATA[regulación génica]]></kwd>
<kwd lng="en"><![CDATA[serum free DNA]]></kwd>
<kwd lng="en"><![CDATA[PMMA]]></kwd>
<kwd lng="en"><![CDATA[DNA methylation]]></kwd>
<kwd lng="en"><![CDATA[polymorphisms]]></kwd>
<kwd lng="en"><![CDATA[sclerostin]]></kwd>
<kwd lng="en"><![CDATA[osteoporosis]]></kwd>
<kwd lng="en"><![CDATA[gene regulation]]></kwd>
</kwd-group>
</article-meta>
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