Genetics components related with anterior cruciate ligament rupture: sports implications

This review presents a replication analysis that seeks to look at single nucleotide genetic polymorphisms (SNPs) that have been associated with anterior cruciate ligament rupture (ACLR) in more than two independent cohorts. We presented a genotypic map and established the alleles that may play a pro...

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Autores:
ARROYO MOYA, WILSON
Rodríguez Buitrago, Jeansy Alonso
Buitrago Espitia, Jorge Enrique
Prieto Mondragon, Laura del Pilar
Ordoñez-Saavedra, Néstor
Araújo, Duarte
Tipo de recurso:
Article of investigation
Fecha de publicación:
2024
Institución:
Universidad de Ciencias Aplicadas y Ambientales U.D.C.A
Repositorio:
Repositorio Institucional UDCA
Idioma:
spa
OAI Identifier:
oai:repository.udca.edu.co:11158/6006
Acceso en línea:
https://repository.udca.edu.co/handle/11158/6006
https://doi.org/10.58727/jshr.97526
Palabra clave:
570 - Biología::576 - Genética y evolución
Polimorfismo Genético
Genética deportiva
Heridas y Lesiones
Heredabilidad
Predisposición genética
Rights
openAccess
License
https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.es
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dc.title.eng.fl_str_mv Genetics components related with anterior cruciate ligament rupture: sports implications
dc.title.spa.fl_str_mv Componentes genéticos relacionados con la ruptura del ligamento cruzado anterior: implicaciones en el deporte
title Genetics components related with anterior cruciate ligament rupture: sports implications
spellingShingle Genetics components related with anterior cruciate ligament rupture: sports implications
570 - Biología::576 - Genética y evolución
Polimorfismo Genético
Genética deportiva
Heridas y Lesiones
Heredabilidad
Predisposición genética
title_short Genetics components related with anterior cruciate ligament rupture: sports implications
title_full Genetics components related with anterior cruciate ligament rupture: sports implications
title_fullStr Genetics components related with anterior cruciate ligament rupture: sports implications
title_full_unstemmed Genetics components related with anterior cruciate ligament rupture: sports implications
title_sort Genetics components related with anterior cruciate ligament rupture: sports implications
dc.creator.fl_str_mv ARROYO MOYA, WILSON
Rodríguez Buitrago, Jeansy Alonso
Buitrago Espitia, Jorge Enrique
Prieto Mondragon, Laura del Pilar
Ordoñez-Saavedra, Néstor
Araújo, Duarte
dc.contributor.author.none.fl_str_mv ARROYO MOYA, WILSON
Rodríguez Buitrago, Jeansy Alonso
Buitrago Espitia, Jorge Enrique
Prieto Mondragon, Laura del Pilar
Ordoñez-Saavedra, Néstor
Araújo, Duarte
dc.subject.ddc.none.fl_str_mv 570 - Biología::576 - Genética y evolución
topic 570 - Biología::576 - Genética y evolución
Polimorfismo Genético
Genética deportiva
Heridas y Lesiones
Heredabilidad
Predisposición genética
dc.subject.decs.none.fl_str_mv Polimorfismo Genético
dc.subject.proposal.none.fl_str_mv Genética deportiva
Heridas y Lesiones
Heredabilidad
Predisposición genética
description This review presents a replication analysis that seeks to look at single nucleotide genetic polymorphisms (SNPs) that have been associated with anterior cruciate ligament rupture (ACLR) in more than two independent cohorts. We presented a genotypic map and established the alleles that may play a protective role in the injury. Similarly, components such as predisposition and heritability to the lesion reported in the literature are observed. The information was obtained from the Scopus, Pubmed, and EBSCO Host (Sportdiscus) databases. Seven SNPs associated with ACLR were identified in two and more independent cohorts (COL1A1 rs1800012, COL3A1 rs1800255, COL5A1 rs12722, COL12A1 rs970547, KDR rs2071559, ACAN rs1516797 y VEGFA rs2010963). On the other hand, the evidence found shows a heritability of 69% for the injury; however, more studies are needed to verify this high percentage because only one study was reported, and it was conducted in a non-athlete population. Likewise, the probability of suffering an ACLR is established between 12% and 30%, when a first-degree relative presented the injury. The genetic component should have a more significant influence in the prediction, follow-up, inclusion in programs, and optimization of post-injury rehabilitation and therapy of athletes at high hereditary risk. © 2024 Didactic Asociation Andalucia
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-08-12T20:04:05Z
dc.date.available.none.fl_str_mv 2024-08-12T20:04:05Z
dc.date.issued.none.fl_str_mv 2024
dc.type.none.fl_str_mv Artículo de revista
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dc.identifier.citation.none.fl_str_mv Arroyo-Moya, W.; Rodríguez-Buitrago, A.; Buitrago-Espitia, J.; Prieto-Mondragón, L.; Ordoñez-Saavedra, N.; Duarte Araujo (2024). Componentes genéticos relacionados con la rupture del ligamento cruzado anterior: Implicaciones en el deporte. Journal of Sport and Health Research. 16(2): 183-196. https://doi.org/10.58727/jshr.97526
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identifier_str_mv Arroyo-Moya, W.; Rodríguez-Buitrago, A.; Buitrago-Espitia, J.; Prieto-Mondragón, L.; Ordoñez-Saavedra, N.; Duarte Araujo (2024). Componentes genéticos relacionados con la rupture del ligamento cruzado anterior: Implicaciones en el deporte. Journal of Sport and Health Research. 16(2): 183-196. https://doi.org/10.58727/jshr.97526
19896239
url https://repository.udca.edu.co/handle/11158/6006
https://doi.org/10.58727/jshr.97526
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dc.relation.ispartofjournal.none.fl_str_mv Journal of Sport and Health Research
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spelling ARROYO MOYA, WILSONvirtual::276-1Rodríguez Buitrago, Jeansy Alonsovirtual::277-1Buitrago Espitia, Jorge Enriquevirtual::278-1Prieto Mondragon, Laura del Pilarvirtual::279-1Ordoñez-Saavedra, Néstorvirtual::280-1Araújo, Duartevirtual::281-12024-08-12T20:04:05Z2024-08-12T20:04:05Z2024Arroyo-Moya, W.; Rodríguez-Buitrago, A.; Buitrago-Espitia, J.; Prieto-Mondragón, L.; Ordoñez-Saavedra, N.; Duarte Araujo (2024). Componentes genéticos relacionados con la rupture del ligamento cruzado anterior: Implicaciones en el deporte. Journal of Sport and Health Research. 16(2): 183-196. https://doi.org/10.58727/jshr.97526https://repository.udca.edu.co/handle/11158/6006https://doi.org/10.58727/jshr.9752619896239This review presents a replication analysis that seeks to look at single nucleotide genetic polymorphisms (SNPs) that have been associated with anterior cruciate ligament rupture (ACLR) in more than two independent cohorts. We presented a genotypic map and established the alleles that may play a protective role in the injury. Similarly, components such as predisposition and heritability to the lesion reported in the literature are observed. The information was obtained from the Scopus, Pubmed, and EBSCO Host (Sportdiscus) databases. Seven SNPs associated with ACLR were identified in two and more independent cohorts (COL1A1 rs1800012, COL3A1 rs1800255, COL5A1 rs12722, COL12A1 rs970547, KDR rs2071559, ACAN rs1516797 y VEGFA rs2010963). On the other hand, the evidence found shows a heritability of 69% for the injury; however, more studies are needed to verify this high percentage because only one study was reported, and it was conducted in a non-athlete population. Likewise, the probability of suffering an ACLR is established between 12% and 30%, when a first-degree relative presented the injury. The genetic component should have a more significant influence in the prediction, follow-up, inclusion in programs, and optimization of post-injury rehabilitation and therapy of athletes at high hereditary risk. © 2024 Didactic Asociation AndaluciaEsta revisión presenta un análisis de replicación que buscó observar los polimorfismos genéticos de un solo nucleótido (SNPs) que han sido asociados con la ruptura del ligamento cruzado anterior (RLCA) en más de dos cohortes independientes. Presentamos un mapa genotípico y establecimos los alelos que pueden cumplir un papel protector de la lesión. De igual manera, se observan componentes como la predisposición y heredabilidad a la lesión reportados en la literatura. La información fue obtenida de las bases de datos Scopus, Pubmed y EBSCO Host (Sportdiscus). Fueron identificados siete SNPs asociados con la RLCA en dos y más cohortes independientes (COL1A1 rs1800012, COL3A1 rs1800255, COL5A1 rs12722, COL12A1 rs970547, KDR rs2071559, ACAN rs1516797 y VEGFA rs2010963). Por otro lado, la evidencia encontrada muestra una heredabilidad del 69% para la lesión, sin embargo, son necesarios más estudios que comprueben este alto porcentaje debido a que solo se reportó un estudio y este fue realizado en población no deportista. Asimismo, la probabilidad de sufrir una RLCA se establece entre en 12% y 30%, cuando un familiar de primer grado presentó la lesión. El componente genético debería tener mayor influencia en la predicción, seguimiento, inclusión en programas y la optimización de la rehabilitación y la terapia posteriores a la lesión de los atletas con alto riesgo hereditario.Incluye referencias bibliográficasapplication/pdfspahttps://creativecommons.org/licenses/by-nc-sa/4.0/legalcode.eshttps://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_abf2https://recyt.fecyt.es/index.php/JSHR/article/view/97526570 - Biología::576 - Genética y evoluciónPolimorfismo GenéticoGenética deportivaHeridas y LesionesHeredabilidadPredisposición genéticaGenetics components related with anterior cruciate ligament rupture: sports implicationsComponentes genéticos relacionados con la ruptura del ligamento cruzado anterior: implicaciones en el deporteArtículo de revistahttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionTexthttp://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85LaReferencia(May.-Ago., 2024)142116Journal of Sport and Health 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jecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.</li>
      <li>
        Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:
        <ol type="i">
          <li>Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.</li>
          <li>Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
        </ol>
      </li>
      <li>Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.</li>
    </ol>
  </li>
  <br/>
  <li>
    Representaciones, Garantías y Limitaciones de Responsabilidad.
    <p>A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Limitación de responsabilidad.
    <p>A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.</p>
  </li>
  <br/>
  <li>
    Término.
    <ol type="a">
      <li>Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.</li>
      <li>Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.</li>
    </ol>
  </li>
  <br/>
  <li>
    Varios.
    <ol type="a">
      <li>Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.</li>
      <li>Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.</li>
      <li>Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.</li>
      <li>Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.</li>
    </ol>
  </li>
  <br/>
</ol>
