Caracterização 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 falciforme
Sickle 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 c...
| Autor principal: | Almeida, Emerson Garcia de |
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| Grau: | Dissertação |
| Idioma: | por |
| Publicado em: |
Universidade do Estado do Amazonas
2020
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| Acesso em linha: |
http://repositorioinstitucional.uea.edu.br//handle/riuea/2240 |
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Sickle 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. |