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dc.contributor.authorAlmeida, Emerson Garcia de-
dc.date.available2020-03-12-
dc.date.available2020-03-12T14:14:05Z-
dc.date.issued2017-11-26-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/2240-
dc.description.abstractSickle cell disease (SCD) is a hereditary blood disorder cause by a point muta- tion in the β-globin chain of hemoglobin (HBB; glu(E)6 val(A); GAG- GTG; rs334). The hallmark abnormality of sickle cell anemia (SCA) is the polymerization of deoxygenated hemoglobin S and aggregation into fibers. This causes drastic change in hemoglobin solubility that leads to heterogeneities in cell shape and density, hemolysis, higher risk of infections and recurrent vaso-occlusive crisis (VOC) with pain, which result in chronic organ damage. Despite being a monogenic disease, patients with SCA have a substantial phenotypic variability. Several single nucleotide polymorphisms (SNPs) in cytokine and inflammasome genes could lead to functional alterations in the transcriptional regulation. Some SNPs in NLRP3 inflammasome could lead at increase of its production causing negative outcomes in diseases. Our study therefore aimed at evaluating SNPs IL-1ß, IL-18, NLRP1 and NLR3 genes frequency and their association with clinical severity in SCA patients. It’s a transversal-descriptive study involved 21 SCA patients and 50 age, sex and ethnicity-matched healthy individuals. The SNPs were identified by PCR-RFLP for IL-1ß (rs187238) and IL-18 (rs16944) genes. The SNPs were identified by Real Time PCR (qPCR) for NLRP1 (rs12150220; rs2670660) and NLRP3(rs10754558; rs35829419) inflammasome genes. Associations between these SNPs and the clinical severity profiles of patients with SCA were then determined. The SNP of NLRP1 and NLRP3 inflammasome genes was not associated with SCA patients. In the same way, The SNP of these inflammasome the SNP’s of IL-1ß and IL-18 genes was not associated with clinical severity in SCA patients. Thus, our work provides evidence that despite SCA being a chronic inflammatory disease, only genes polymorphisms are not enough to change the outcome of this disease.pt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.rightsAtribuição-NãoComercial-SemDerivados 3.0 Brasil*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/br/*
dc.subjectAnemia falciformept_BR
dc.subjectHematologiapt_BR
dc.titleCaracterização dos polimorfismos dos genes dos receptores dos inflamassomas NLRP1 e NLRP3 e das interleucinas il-1ß e il-18 e suas relações com o escore de gravidade em portadores de anaemia falciformept_BR
dc.title.alternativeCharacterization of the polymorphisms of the NLRP1 and NLRP3 inflammasome receptor genes and of the interleukins il-1ß and il-18 and their relationship with the severity score in patients with sickle cell anemiapt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2020-03-12T14:14:05Z-
dc.contributor.advisor-co1Paula, Erich Vinicius de-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/0983518713985469pt_BR
dc.contributor.advisor1Marie, Adriana Malheiro Alle-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.contributor.referee1Marie, Adriana Malheiro Alle-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/2627415957053194pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/9145494570288954pt_BR
dc.description.resumoA anemia falciforme (A.F.) é uma doença hereditária causada por um ponto de mutação na cadeia da ß-globina que resulta na substituição do àcido glutâmico pela valina na posição 6 do gene (HBB; glu(E)6 val(A); GAG-GTG; rs334). A anormalidade símbolo da A.F. é a agregação e polimerização da hemoglobina S desoxigenada. Isto resulta numa drástica mudança na solubilidade da hemoglobina que leva assumir a forma de foice, responsável por crises vaso oclusivas recorrentes acompanhadas de dor, que resultam em lesões crônicas em órgãos e tecidos Apesar de ser uma doença monogênica, portadores de anemia falciforme tem uma substancial variedade fenotípica no qual indivíduos com o mesmo genótipos apresentam diferentes graus de gravidade. Vários polimorfismos de nucleotídeo único (SNPs) nos genes que codificam as citocinas (IL) e os inflamossomas (NLRPs) podem levar a alterações funcionais na regulação transcripcional. Alguns SNPs do NLRP3 levam a produção excessiva de IL-1ß que pode causar impacto negativo em diversas doenças. Especificamente, IL-1ß E IL-18 são importantes na resposta inflamatória aguda e seus SNPs tem sido considerados como preditores de prognóstico em varias condições inflamatórias. Nosso estudo tem como objetivo avaliar a frequência dos SNP’s no gene dos inflamossomas NLRP1 e NLRP3 e nos genes das IL-1ß e IL-18 e sua associação com os perfis clínicos de gravidade em indivíduos portadores de anemia falciforme. É um estudo descritivo transversal envolvendo 21 pacientes portadores de anemia falciforme (grupo de casos) e 50 indivíduos sadios (grupo de controles). Os SNPs dos genes das IL-1ß (rs187238) e IL-18 (rs16944) foram identificados pela técnica de RFLP-PCR. Os SNPS dos genes dos inflamossomas NLRP1 (rs12150220; rs2670660) e NLRP3(rs10754558; rs35829419) foram identificados pela técnica de PCR em tempo real (qPCR). A associação entre esse SNPs e os fenótipos de gravidade clínica dos indivíduos portadores de anemia falciforme foram determinados. Não houve associação dos polimorfismos dos genes dos inflamossomas NLRP1 e NLRP3 com indivíduos portadores de anemia falciforme em nosso grupo de estudo, assim como não houve associação desses com os polimorfismos dos genes das Interleucinas IL-1ß e IL-18 com os fenótipos de gravidades em indivíduos portadores de anemia falciforme. Em conjunto, os dados aqui apresentados constituem na afirmação de que apesar da anemia falciforme ser uma doença de caráter inflamatório crônico, só os polimorfismos de genes que influenciam na resposta imune não suficientes para alterar o curso da gravidade da apresentação clínica.pt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS Á HEMATOLOGIApt_BR
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