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dc.contributor.authorXabregas, Lilyane de Amorim-
dc.date.available2022-08-10-
dc.date.available2022-08-11T17:01:20Z-
dc.date.issued2020-07-29-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4124-
dc.description.abstractAcute lymphoblastic leukemia (ALL) is the most common hematological neoplasm and the main cause of childhood mortality. Single Nucleotide Polymorphisms (SNPs) in key molecules of the immune system, such as Toll-Like receptors, are associated with the development of various diseases, however, their role in ALL is unknown. Objective: In this study, we described the frequency of Toll-Like receptor polymorphisms in patients with acute lymphoblastic leukemia and their association with clinical prognosis. Material and Methods: A case-control study was carried out with 152 DNA samples from patients with ALL and 187 samples from individuals without the disease (control group). Genotypic and allelic discrimination was performed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method (PCR-RFLP) for the TLR1 S602I (rs5743618), TLR4 A299G and I399T (rs4986790 and rs4986791), TLR5 R392S (rs5744105), TLR6 S249P (rs5743810), TLR9 -1237C/T and -1486C/T (rs5743836 and rs187084) and CD14 -159 (rs2569191) polymorphisms. Descriptive and statistical analysis was performed using Microsoft Excel 2013 and GraphPad Prism v.5.0 software. Results: The C/C genotype from -1486C/T polymorphism (TLR9) was associated with the risk of development acute lymphoblastic leukemia (TLR9: T/T + C/T vs. C/C OR = 2.0 [95% CI: 1.1 -3.5, p=0.01]; C/T vs. C/C OR = 2.2 [95% CI: 1.2–4.1, p=0.00]). In addition, the T/T genotype from - 1486 C/T (TLR9) was associated with the presence of comorbidities on diagnosis (TLR9: T/T C/T vs. C/C OR = 2.1 [95% CI: 1.1- 4.3, p=0.04]; T/T vs. C/T OR = 2.2 [95% CI: 1.0-4.7, p=0.04]). Conclusion: Our findings suggested a significant role for SNP -1486 C/T (TLR9) without the development and presence of infectious comorbidities in acute lymphoblastic leukemiapt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectLeucemia Linfoide Agudapt_BR
dc.subjectImunidade Inatapt_BR
dc.subjectSNPspt_BR
dc.subjectTLRspt_BR
dc.subjectAcute lymphoid leukemiapt_BR
dc.titleEstudo dos polimorfismos nos genes dos TLRS em pacientes diagnósticados com Leucemia Linfoide Aguda (LLA)pt_BR
dc.title.alternativeStudy of polymorphisms in TLRS genes in patients diagnosed with Acute Lymphoblastic Leukemia (ALL)pt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2022-08-11T17:01:20Z-
dc.contributor.advisor-co1Marie, Adriana Malheiro Alle-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.contributor.advisor1Costa, Allyson Guimarães da-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/7531662673281014pt_BR
dc.contributor.referee1Passos, Leny Nascimento da Motta-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/8194622149198642pt_BR
dc.contributor.referee2Mourão , Lucivania Prata de Souza-
dc.contributor.referee2Latteshttp://lattes.cnpq.br/1135734404648095pt_BR
dc.contributor.referee3Ramasawmy, Rajendranath-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/3420417277915974pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/1826922829844542pt_BR
dc.description.resumoAs Leucemias Agudas são neoplasias malignas graves, que acometem crianças e adultos e tem grande incidência no Amazonas. Sua etiologia e patogênese ainda permanecem incertas, sendo considerada uma doença multifatorial. Frente, a essa necessidade de informações, autores como, Leo Kinlen e Mel Greaves, tem sugerido, por meio de ponto vistas diferentes, que o modo como o sistema imunológico de alguns indivíduos reconhece antígenos e responde aos mesmos representa um fator de risco para a leucogênese. Polimorfismos nos genes dos receptores TLRs, presentes na imunidade inata, podem conter grande influência na alteração do padrão de resposta do indivíduo, contribuindo para a resistência ou suscetibilidade de doenças infecciosas. Objetivo: Assim, nosso objetivo foi de avaliar a influência dos polimorfismos nos genes dos receptores TLRs no prognostico clínico de pacientes diagnosticados com Leucemia Linfoide Aguda (LLA). Material e Métodos: Um estudo de caso- controle foi realizado com 152 amostras de DNA de pacientes com LLA e 187 amostras de indivíduos sem a doença (grupo controle). A discriminação genotípica e alélica foi realizada pelo método PCR-RFLP dos SNPs rs5743618 (TLR1 S602I), rs4986790 e rs4986791 (TLR4 A299G e I399T), rs5744105 (TLR5 R392S), rs5743810 (TLR6 S249P), rs5743836 e rs187084 (TLR9 -1237C/T e -1486C/T) e molécula rs2569191 (CD14 -159). A análise descritiva e estatística foi realizada com os softwares Microsoft Excel 2013 e GraphPadPrism v.5.0. Resultados: O genótipo C/C do polimorfismo -1486 C/T (TLR9) foi associado com o risco de desenvolvimento de leucemia linfoide aguda (TLR9: T/T+C/T vs. C/C OR = 2,0 [95% CI: 1,1-3,5, p = 0,014]; C/T vs. C/C OR = 2,2, [IC 95%: 1,2–4,1, p = 0,006]). Além disso, o genótipo TT do SNP -1486 C/T (TLR9) foi associado com a presença de comorbidades ao diagnóstico (TLR9: T/T + C/T vs. C/C OR = 2,1 [95% CI: 1,1-4,3, p=0,04]; T/T vs. C/T OR = 2,2 [95% CI: 1,0-4,7, p=0,04]). Conclusão: Nossos achados sugerem um papel significativo do SNP -1486C/T (TLR9) no desenvolvimento e presença de comorbidades infecciosas na leucemia linfoide agudapt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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