Author | Silvino, Ana Carolina Rios | |
Author | Costa, Gabriel Luiz | |
Author | Araújo, Flávia Carolina Faustino de | |
Author | Ascher, David Benjamin | |
Author | Pires, Douglas Eduardo Valente | |
Author | Fontes, Cor Jesus Fernandes | |
Author | Carvalho, Luzia Helena | |
Author | Brito, Cristiana Ferreira Alves de | |
Author | Sousa, Taís Nóbrega de | |
Access date | 2017-07-04T18:53:35Z | |
Available date | 2017-07-04T18:53:35Z | |
Document date | 2016 | |
Citation | SILVINO, Ana Carolina Rios et al. Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses. PLoS One, v. 11, n. 7. art. e0160172, 2016. | pt_BR |
ISSN | 1932-6203 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/19714 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Plasmodium vivax | pt_BR |
Title | Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses | pt_BR |
Type | Article | pt_BR |
Abstract | Although Plasmodium vivax relapses are classically associated with hypnozoite activation, it has been proposed that a proportion of these cases are due to primaquine (PQ) treatment failure caused by polymorphisms in cytochrome P-450 2D6 (CYP2D6). Here, we present evidence that CYP2D6 polymorphisms are implicated in PQ failure, which was reinforced by findings in genetically similar parasites, and may explain a number of vivax relapses. Using a computational approach, these polymorphisms were predicted to affect the activity of CYP2D6 through changes in the structural stability that could lead to disruption of the PQ-enzyme interactions. Furthermore, because PQ is co-administered with chloroquine (CQ), we investigated whether CQ-impaired metabolism by cytochrome P-450 2C8 (CYP2C8) could also contribute to vivax recurrences. Our results show that CYP2C8-mutated patients frequently relapsed early (<42 days) and had a higher proportion of genetically similar parasites, suggesting the possibility of recrudescence due to CQ therapeutic failure. These results highlight the importance of pharmacogenetic studies as a tool to monitor the efficacy of antimalarial therapy. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Pesquisa em Informatica de Biosistemas. Belo Horizonte, MG, Brazil/University of Cambridge. Department of Biochemistry. Cambridge, United Kingdom | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Pesquisa em Informatica de Biosistemas. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Universidade Federal de Mato Grosso. Hospital Julio Muller Cuiabá, MT, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil | pt_BR |
Subject | Plasmodium vivax | pt_BR |
Subject | antimalarial therapy | pt_BR |
e-ISSN | 10.1371/journal.pone.0160172 | |