Patrones de metilación de ADN en sangre periférica en periodontitis y enfermedad de Alzheimer: análisis diferencial, de intersección y validación

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dc.contributor.advisorHernández Hincapié, Hernán Guillermo
dc.contributor.advisorNaranjo Galvis, Carlos Andrés
dc.contributor.authorChacón Arboleda, Paula Tatiana
dc.coverage.campusCRAI-USTA Bucaramangaspa
dc.date.accessioned2024-12-05T14:55:15Z
dc.date.available2024-12-05T14:55:15Z
dc.date.issued2024-12-04
dc.descriptionLa presente tesis de doctorado analizó patrones de metilación de ADN en sangre periférica en pacientes con enfermedad de Alzheimer (EA) y periodontitis a lo largo del genoma, revelando alteraciones epigenéticas en genes clave relacionados con inflamación y rutas metabólicas. En periodontitis, se encontraron posiciones y regiones con metilación diferencial, identificándose genes diferencialmente hipermetilados como GDAP2, RPH3AL, SLC19A1 y COL18A1; y genes diferencialmente hipometilados como CUL3, ARID3C, BCL11A y SLC6A5, implicados en la respuesta inmune y el metabolismo. En EA, se encontraron posiciones y regiones con metilación diferencial, incluyendo genes diferencialmente hipermetilados como CACNA1A, HOXA-AS3, HOXA6, y diferencialmente hipometilados como MIB2, KMT5A, MIDEAS y BCAM, involucrados en la inflamación sistémica. El análisis de enriquecimiento génico funcional mostró ontologías relacionadas con transporte celular y respuesta inmune en periodontitis y EA. De forma interesante, se encontró una coincidencia epigenética exacta en una región de 93 pares de bases del gen MDGA1 en EA y periodontitis, indicando relevancia epigenética en la intersección entre estas enfermedades. Asimismo, los resultados de metilación diferencial para genes priorizados evidenciaron a HLA-B y PDGFRA en ambas enfermedades indicando una conexión epigenética inflamatoria entre ellas. Los CpG sustitutos de cerebro en sangre que se encontraron metilados diferencialmente en EA se asociaron con los genes protocadherina PCDHGB1-3 y PCDHGA1-6. La validación en pacientes colombianos mostró diferencias significativas en la metilación de MDGA1, GDAP2 y MIB2. Estos hallazgos sugieren que la metilación diferencial desempeña un papel en la patogénesis compartida entre periodontitis y EA, justificando nuevas exploraciones de estos mecanismos epigenéticos comunes.spa
dc.description.abstractThis PhD thesis analyzed DNA methylation patterns in peripheral blood in patients with Alzheimer's disease (AD) and periodontitis throughout the genome, revealing epigenetic alterations in key genes related to inflammation and metabolic pathways. In periodontitis, positions and regions with differential methylation were found, identifying differentially hypermethylated genes such as GDAP2, RPH3AL, SLC19A1 and COL18A1; and differentially hypomethylated genes such as CUL3, ARID3C, BCL11A and SLC6A5, involved in immune response and metabolism. In AD, positions and regions with differential methylation were found, including differentially hypermethylated genes such as CACNA1A, HOXA-AS3, HOXA6, and differentially hypomethylated genes such as MIB2, KMT5A, MIDEAS and BCAM, involved in systemic inflammation. Functional gene enrichment analysis showed ontologies related to cellular transport and immune response in periodontitis and AD. Interestingly, an exact epigenetic match was found in a 93-base pair region of the MDGA1 gene in AD and periodontitis, indicating epigenetic relevance at the intersection between these diseases. Likewise, differential methylation results for prioritized genes showed HLA-B and PDGFRA in both diseases showing an inflammatory epigenetic connection between them. The blood-brain surrogate CpGs found differentially methylated in AD were associated with the protocadherin genes PCDHGB1-3 and PCDHGA1-6. Validation in Colombian patients showed significant differences in the methylation of MDGA1, GDAP2, and MIB2. These findings suggest that differential methylation plays a role in the shared pathogenesis between periodontitis and AD, justifying further explorations of these common epigenetic mechanisms.spa
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Odontologíaspa
dc.description.domainhttps://www.ustabuca.edu.co/spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.citationChacón Arboleda, P. T. (2024) Patrones de metilación de ADN en sangre periférica en periodontitis y enfermedad de Alzheimer: análisis diferencial, de intersección y validación. [Tesis de posgrado]. Universidad Santo Tomás, Bucaramanga, Colombiaspa
dc.identifier.instnameinstname:Universidad Santo Tomásspa
dc.identifier.reponamereponame:Repositorio Institucional Universidad Santo Tomásspa
dc.identifier.repourlrepourl:https://repository.usta.edu.cospa
dc.identifier.urihttp://hdl.handle.net/11634/58784
dc.language.isospaspa
dc.publisherUniversidad Santo Tomásspa
dc.publisher.facultyFacultad de Odontologíaspa
dc.publisher.programDoctorado Odontologíaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.coarhttp://purl.org/coar/access_right/c_14cbspa
dc.rights.localAbierto (Texto Completo)spa
dc.subject.keywordDNA methylationspa
dc.subject.keywordEpigenomicsspa
dc.subject.keywordPeriodontitisspa
dc.subject.keywordAlzheimer's diseasespa
dc.subject.keywordBiomarkersspa
dc.subject.lembPatrones de metilación de ADNspa
dc.subject.lembPacientes con enfermedad de Alzheimerspa
dc.subject.lembEnfermedades de los dientesspa
dc.subject.lembPatogénesisspa
dc.subject.lembAnálisis de informaciónspa
dc.subject.proposalMetilación de ADNspa
dc.subject.proposalEpigenómicaspa
dc.subject.proposalPeriodontitisspa
dc.subject.proposalenfermedad de Alzheimerspa
dc.subject.proposalBiomarcadoresspa
dc.titlePatrones de metilación de ADN en sangre periférica en periodontitis y enfermedad de Alzheimer: análisis diferencial, de intersección y validaciónspa
dc.type.categoryFormación de Recurso Humano para la Ctel: Tesis de Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06spa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.driveinfo:eu-repo/semantics/doctoralThesis
dc.type.localTesis doctoralspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersion

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