Caracteriza????o molecular de isoformas do citocromo P450 em pacientes com mal??ria por Plasmodium vivax

• Author(s): Jesus, Jaquelane Silva de
• Date: 2015
• Origin: Oasisbr
• Subject(s): Isoformas do citocromo P450; Mal??ria Plasmodium viva - Pacientes; Polymorphism; Cytochrome P450; Vivax mal??ria; CI??NCIAS DA SA??DE: FARM??CIA
• Document Type: Master thesis
• Language: Portuguese

Description

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CAPES - Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior

High prevalence in Brazil, specifically in the Amazon Region, mal??ria is a parasitic infectious disease with socioeconomic impact sin endemic areas. Plasmodium vivax is the most prevalent agent and has been associated with cases of severe mal??ria before attributed only to Plasmodium falciparum. Genetic variability in host metabolism of antimal??rial drugs, influenced by the polymorphism of cytochrome P450(CYP), could lead to significant changes in antimal??rial treatment response. Little is known about the influence of genetic factors in the increase of the individual susceptibility of the host to development of severe disease. Therefore, this project aimed to determine the frequency of alleles CYP2B6*6, CYP2C8*3 and CYP2D6*4 in patients with vivax mal??ria, to evaluate the relationship between the alleles found and the occurrence of severe mal??ria and further establish the hematological and biochemical profile among carriers of alleles found. Therefore, we used peripheral blood samples of patients with vivax mal??ria treated at a health care reference in Manaus-AM. Which were extracted leukocyte DNA, which in turn were amplified by real-time PCR using TaqMan ?? system for allelic discrimination. The frequencies of the alleles CYP2B6*6, CYP2C8*3 and CYP2D6*4 were 28.26%, 6.7%, 8.87%, respectively. The CYP2D6*4 allele was more prevalent among patients diagnosed with severe vivax mal??ria, and was associated with normal levels of reticulocytes, erythrocytes and hematocrit. Future studies are needed to understand the clinical implications of the polymorphisms found in patients with vivax mal??ria.

De elevada preval??ncia no Brasil, especificamente na Regi??o Amaz??nica, a mal??ria ?? uma doen??a infecto-parasit??ria com impactos socioecon??micos em ??reas end??micas. O Plasmodium vivax ?? o agente de maior preval??ncia e tem sido associado a casos graves de mal??ria antes atribu??da apenas ao Plasmodium falciparum. A variabilidade gen??tica do hospedeiro no metabolismo de f??rmacos antimal??ricos, influenciada pelo polimorfismo de isoformas do citocromo P450 (CYP), poderia levar a altera????es significativas na resposta terap??utica antimal??rica. Pouco se conhece sobre a influ??ncia dos fatores gen??ticos no aumento da susceptibilidade individual do hospedeiro ao desenvolvimento de formas graves da doen??a. Portanto este projeto objetivou determinar a frequ??ncia dos alelos CYP2B6*6, CYP2C8*3 e CYP2D6*4 em pacientes com mal??ria vivax, avaliar a rela????o entre os alelos encontrados e a ocorr??ncia de mal??ria grave e ainda estabelecer o perfil hematol??gico e bioqu??mico entre os portadores dos alelos encontrados. Para tanto foram utilizadas amostras de sangue perif??rico de pacientes com mal??ria vivax atendidos numa unidade de sa??de de refer??ncia na cidade de Manaus-AM. Dos quais foram extra??dos o DNA leucocit??rio, que por sua vez foram amplificado por PCR em tempo real usando o sistema TaqMan?? para a discrimina????o al??lica. As freq????ncias dos alelos CYP2B6*6, CYP2C8*3 e CYP2D6*4 foram 28,26%, 6,7%, 8,87%, respectivamente. O alelo CYP2D6*4 foi o mais prevalente entre os pacientes diagnosticados com mal??ria vivax grave, e tamb??m foi associado a n??veis normais de reticul??citos, eritr??citos e hemat??crito. Estudos futuros s??o necess??rios para compreender as implica????es cl??nicas dos polimorfismos encontrados em pacientes com mal??ria vivax.