Doctorado Odontología

URI permanente para esta colecciónhttp://hdl.handle.net/11634/13212

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    Ítem
    Patrones de metilación de ADN en sangre periférica en periodontitis y enfermedad de Alzheimer: análisis diferencial, de intersección y validación
    (Universidad Santo Tomás, 2024-12-04) Chacón Arboleda, Paula Tatiana; Hernández Hincapié, Hernán Guillermo; Naranjo Galvis, Carlos Andrés
    This 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.
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    Ítem
    Patrones de metilación del ADN de genes vinculados al inflamasoma NLRP3 asociados a tipos específicos celulares en periodontitis y diabetes mellitus Tipo 2
    (Universidad Santo Tomás, 2023-10-05) Cárdenas Gutiérrez, Angélica María; Hernández Hincapié, Hernán Guillermo; Arango Rodríguez, Martha Ligia
    Introduction: Periodontitis 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.