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dc.contributor.authorMacêdo, Marielle Machado-
dc.date.available2023-03-09-
dc.date.available2023-03-20T15:37:22Z-
dc.date.issued2023-09-29-
dc.identifier.urihttp://repositorioinstitucional.uea.edu.br//handle/riuea/4598-
dc.description.abstractIn the Amazon, Plasmodium vivax (P. vivax) infection is more prevalent, and its treatment includes primaquine (PQ), a hypnozoiticide drug. However, its use is limited by the risk of acute hemolytic anemia (AHA) in glucose-6-phosphate dehydrogenase (dG6PD) deficient individuals, with a frequency of 4.5% to 10% in the Amazon region. Interaction with cytochrome P450 (CYP) liver enzymes, some pharmacogenes such as CYP2C19, CYP2D6 and CYP3A4 associated with PQ metabolism can significantly enhance or reduce its biotransformation. This study aims to evaluate the influence of CYP2C19, CYP2D6 and CYP3A4 variants on hemolysis in G6PD-deficient and non-G6PD-deficient individuals treated with primaquine for P. vivax. We included 18 patients of both sexes, > 6 months of age treated with PQ, diagnosed with vivax malaria and hemolysis. Phenotyping for G6PD was performed using the SD Biosensor and genotyping for G6PD and CYPs using the real-time PCR technique. Of these, 55.6% had the African A- variant (G202A/A376G ), 11.1% the African A+ (A376G), 5.6% the Mediterranean (C563T) and 27.8% were wild type. Genotyping of CYP2C19, CYP2D6 and CYP3A4 did not show statistical significance in the frequency of star alleles between groups (p >0.05). Elevated levels of hepatic and renal markers were observed in normal (gNM), rapid (gRM) and ultra-rapid (gUM) metabolizers of CYP2C19 and CYP2D6 in dG6PD (p < 0.05). CYP3A4 *1/*1B genotype had greater clinical impact in both groups, although not significant (p >0.05). These findings reinforce the importance of studies on the mapping of G6PD deficiency and genetic variants of CYP2C19, CYP2D6 and CYP3A4, which will allow validating the prevalence and determining the influence of CYPs on the hemolytic process of individuals with vivax malaria, and will contribute to a more adequate, avoiding complications caused by the metabolism of PQ in CYPpt_BR
dc.languageporpt_BR
dc.publisherUniversidade do Estado do Amazonaspt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectPlasmodium vivaxpt_BR
dc.subjectMaláriapt_BR
dc.subjectHemólise por primaquinapt_BR
dc.subjectDeficiência G6PDpt_BR
dc.subjectCitocromo P450pt_BR
dc.subjectprimaquine hemolysispt_BR
dc.titleResposta terapêutica da primaquina em malária vivax - influência de variantes genéticas de G6PD, CYP2C19, CYP2D6 e CYP3A4pt_BR
dc.title.alternativePrimaquine therapeutic response in vivax malaria - influence of genetic variants of G6PD, CYP2C19, CYP2D6 and CYP3A4pt_BR
dc.typeDissertaçãopt_BR
dc.date.accessioned2023-03-20T15:37:22Z-
dc.contributor.advisor-co1Almeida, Anne Cristine Gomes de Almeida-
dc.contributor.advisor-co1Latteshttp://lattes.cnpq.br/6671314609049426pt_BR
dc.contributor.advisor1Melo, Gisely Cardoso de-
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/5566457348830121pt_BR
dc.contributor.referee1Silva, George Allan Villarouco da-
dc.contributor.referee1Latteshttp://lattes.cnpq.br/1939667501234091pt_BR
dc.contributor.referee2Soares, Fernanda Rodrigues-
dc.contributor.referee3Brasil, Larissa Wanderley-
dc.contributor.referee3Latteshttp://lattes.cnpq.br/2360198212821551pt_BR
dc.creator.Latteshttp://lattes.cnpq.br/7735375165517686pt_BR
dc.description.resumoNa Amazônia, a infecção por Plasmodium vivax (P. vivax) é mais prevalente, e seu tratamento inclui a primaquina (PQ), uma droga hipnozoiticida. No entanto, seu uso é limitado pelo risco de anemia hemolítica aguda (AHA) em indivíduos deficientes da glicose-6-fosfato desidrogenase (dG6PD), com frequência de 4,5% a 10% na região Amazônica. A interação com enzimas hepáticas do citocromo P450 (CYP), de alguns farmacogenes como CYP2C19, CYP2D6 e CYP3A4 associados ao metabolismo da PQ podem intensificar ou reduzir significativamente sua biotransformação. Este estudo visa avaliar a influência das variantes de CYP2C19, CYP2D6 e CYP3A4 na hemólise em deficientes e não deficientes de G6PD, tratados com primaquina para P. vivax. Foram incluídos 18 pacientes de ambos os sexos, > 6 meses de idade tratados com PQ, com diagnóstico de malária vivax e hemólise. Foi realizada fenotipagem para G6PD através do SD Biosensor e genotipagem para G6PD e CYPs utilizando a técnica de real-time PCR. Destes, 55,6% apresentaram a variante Africana A- (G202A/A376G), 11,1% a Africana A+ (A376G), 5,6% a Mediterrânea (C563T) e 27,8% eram tipo selvagem. A genotipagem de CYP2C19, CYP2D6 e CYP3A4 não mostrou significância estatística na frequência de alelos estrela entre os grupos (p >0,05). Níveis elevados de marcadores hepáticos e renais foram observados em metabolizadores normais (gNM), rápidos (gRM) e ultrarrápidos (gUM) de CYP2C19 e CYP2D6 em dG6PD (p <0,05). O genótipo *1/*1B de CYP3A4 teve maior impacto clínico em ambos os grupos, apesar de não significativo (p >0,05). Esses achados reforçam a importância de estudos sobre o mapeamento da deficiência de G6PD e variantes genéticas de CYP2C19, CYP2D6 e CYP3A4, que permitirão validar prevalência e determinar a influência das CYPs no processo hemolítico de indivíduos com malária vivax, e contribuirão com um esquema terapêutico mais adequado, evitando complicações ocasionadas pela metabolização da PQ em CYPpt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.programPPGH -PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS APLICADAS À HEMATOLOGIApt_BR
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