Patrones de metilación del ADN de genes vinculados al inflamasoma NLRP3 asociados a tipos específicos celulares en periodontitis y diabetes mellitus tipo 2

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dc.contributor.advisorHernández Hincapié, Hernán Guillermo
dc.contributor.advisorArango Rodríguez, Martha Ligia
dc.contributor.authorCárdenas Gutiérrez, Angélica María
dc.date.accessioned2023-10-06T20:13:58Z
dc.date.available2023-10-06T20:13:58Z
dc.date.issued2023-10-05
dc.descriptionLa periodontitis y la diabetes son enfermedades que se caracterizan por el desarrollo de una respuesta inmune desregulada que produce resorción ósea y resistencia a la insulina respectivamente. Debido a la respuesta inflamatoria acumulada a nivel local, provocada por la destrucción de los tejidos periodontales, y la traslocación sistémica de mediadores inflamatorios la periodontitis se asocia con enfermedades como la diabetes. Las modificaciones epigenéticas pueden dar lugar a una diferencia de expresión genética, permitiendo variaciones en los patrones de metilación de ADN entre individuos con Periodontitis y DM2 para diversos tipos celulares. Objetivo: Evaluar los patrones de metilación del ADN de genes vinculados al inflamasoma NLRP3 asociados a monocitos y neutrófilos en periodontitis y diabetes mellitus Tipo 2. Métodos: Estudio de corte transversal. Incluía dos fases: Fase 1, Análisis de microarreglos in silico. Fase 2, estudio de validación de células aisladas de individuos con periodontitis y/o diabetes mellitus.Muestra: Pacientes entre 19 y 65 años con periodontitis que contengan datos de microarreglos de metilación de ADN-Infinium® HumanDNA Methylation 450K y diabetes (HbA1c ≥ 6.5%).Se normalizaron los datos con SWAN y las posiciones y regiones diferencialmente metiladas se analizaron con Limma y DMRcat. Se realizó un análisis de regresión logístico bivariado y multivariado para el control de las variables de confusión tales como: sexo, edad, tabaquismo, IMC y dislipidemia. Se consideró un valor de p˂0.05 estadísticamente significativo. Resultados: Genes HLA-DQB1, HLA-DQA1 HLA-DRB1, RNF39, COL5A1, PMEPA1, CCDC144NL, CACNA1A, EPH4A y PSORS1C1 demostraron metilación diferencial especifica en monocitos y neutrófilos, constituyéndose como marcadores importantes, a ser puestos a prueba en estudios de susceptibilidad/progresión de periodontitis y diabetes. Conclusiones: Las modificaciones de metilación del DNA podrían estar relacionadas con estilos de vida poco saludables que sometan a las células a una reprogramación epigenética que contribuya al mantenimiento de la inflamación.spa
dc.description.abstractPeriodontitis and diabetes are diseases that are characterized by the development of a deregulated immune response that produces bone resorption and insulin resistance respectively. Due to the locally accumulated inflammatory response, caused by the destruction of periodontal tissues and the systemic translocation of inflammatory mediators, periodontitis is associated with systemic diseases such as diabetes. Epigenetic modifications can lead to a difference in gene expression, allowing variations in DNA methylation patterns between individuals with periodontitis and T2DM for various cell types. Objective: To evaluate the DNA methylation patterns of genes linked to the NLRP3 inflammasome associated with monocytes and neutrophils in periodontitis and type 2 diabetes mellitus. Methods: Cross-sectional study. It includes two phases: Phase 1, In silico microarray analysis. Phase 2, validation study of cells isolated from individuals with periodontitis and/or diabetes mellitus. Sample: Patients 19 to 65 years old with periodontitis containing DNA methylation microarray data: Infinium® HumanDNA Methylation 450K and diabetes (HbA1c ≥ 6.5%). Data were normalized with SWAN and differentially methylated positions and regions were analyzed with Limma and DMRcate. A bivariate and multivariate logistic regression analysis was performed to control for confounding variables such as: sex, age, smoking, BMI, and dyslipidemia. A statistically significant value of p˂0.05 was demonstrated. Results: The genes HLA-DQB1, HLA-DQA1 HLA-DRB1, RNF39, COL5A1, PMEPA1, CCDC144NL, CACNA1A, EPH4A and PSORS1C1 demonstrated specific differential methylation in monocytes and neutrophils, becoming important markers to test in susceptibility or progression of periodontitis and diabetes. Conclusions: DNA methylation modifications could be related to unhealthy lifestyles that subject cells to epigenetic reprogramming that contributes to the maintenance of inflammation.spa
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Odontologíaspa
dc.description.domainhttps://www.ustabuca.edu.co/spa
dc.format.mimetypeapplication/pdf
dc.identifier.citationCárdenas Gutiérrez, A. M.( 2023). Patrones de metilación del ADN de genes vinculados al inflamasoma NLRP3 asociados a tipos específicos celulares en periodontitis y diabetes mellitus Tipo 2. [Tesis de Postgrado]. 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/11634/52632
dc.language.isospa
dc.publisherUniversidad Santo Tomásspa
dc.publisher.branchCRAI-USTA Bucaramangaspa
dc.publisher.facultyFacultad de Odontologíaspa
dc.publisher.programDoctorado Odontologíaspa
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dc.rightsAtribución-NoComercial-SinDerivadas 2.5 Colombia
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.coarhttp://purl.org/coar/access_right/c_14cbspa
dc.rights.localAbierto (Texto Completo)spa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.subject.keywordDiabetesspa
dc.subject.keywordPeriodontitisspa
dc.subject.keywordEpigeneticsspa
dc.subject.keywordDNA methylationspa
dc.subject.lembBoca- Enfermedadesspa
dc.subject.lembEnfermedades de los dientesspa
dc.subject.lembTejidos periodontalesspa
dc.subject.proposalEpigenéticaspa
dc.subject.proposalPeriodontitisspa
dc.subject.proposalDiabetesspa
dc.subject.proposalMetilación de ADNspa
dc.titlePatrones de metilación del ADN de genes vinculados al inflamasoma NLRP3 asociados a tipos específicos celulares en periodontitis y diabetes mellitus tipo 2spa
dc.type.categoryFormación de Recurso Humano para la Ctel: Tesis de Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06
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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