Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses

Detalhes bibliográficos
Autor(a) principal: Silvino, Ana Carolina Rios
Data de Publicação: 2016
Outros Autores: Costa, Gabriel Luiz, Araújo, Flávia Carolina Faustino de, Ascher, David Benjamin, Pires, Douglas Eduardo Valente, Fontes, Cor Jesus Fernandes, Carvalho, Luzia Helena, Brito, Cristiana Ferreira Alves de, Sousa, Taís Nóbrega de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/19714
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil
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spelling Silvino, Ana Carolina RiosCosta, Gabriel LuizAraújo, Flávia Carolina Faustino deAscher, David BenjaminPires, Douglas Eduardo ValenteFontes, Cor Jesus FernandesCarvalho, Luzia HelenaBrito, Cristiana Ferreira Alves deSousa, Taís Nóbrega de2017-07-04T18:53:35Z2017-07-04T18:53:35Z2016SILVINO, 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, 2016.1932-6203https://www.arca.fiocruz.br/handle/icict/1971410.1371/journal.pone.0160172engPublic Library of SciencePlasmodium vivaxPlasmodium vivaxantimalarial therapyVariation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapsesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, BrasilFundação 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 KingdomFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Grupo de Pesquisa em Informatica de Biosistemas. Belo Horizonte, MG, BrazilUniversidade Federal de Mato Grosso. Hospital Julio Muller Cuiabá, MT, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, BrasilAlthough 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/19714/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALVariation in Human Cytochrome P-450 Drug-Metabolism Genes_ A Gateway to the Understanding of Plasmodium vivax Relapses - pone.pdfVariation in Human Cytochrome P-450 Drug-Metabolism Genes_ A Gateway to the Understanding of Plasmodium vivax Relapses - pone.pdfapplication/pdf5199113https://www.arca.fiocruz.br/bitstream/icict/19714/2/Variation%20in%20Human%20Cytochrome%20P-450%20Drug-Metabolism%20Genes_%20A%20Gateway%20to%20the%20Understanding%20of%20Plasmodium%20vivax%20Relapses%20-%20pone.pdf3de7aae9f22738fbbff5816b6cbd50bcMD52TEXTVariation in Human Cytochrome P-450 Drug-Metabolism Genes_ A Gateway to the Understanding of Plasmodium vivax Relapses - 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dc.title.pt_BR.fl_str_mv Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
title Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
spellingShingle Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
Silvino, Ana Carolina Rios
Plasmodium vivax
Plasmodium vivax
antimalarial therapy
title_short Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
title_full Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
title_fullStr Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
title_full_unstemmed Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
title_sort Variation in Human Cytochrome P-450 Drug-Metabolism Genes: A Gateway to the Understanding of Plasmodium vivax Relapses
author Silvino, Ana Carolina Rios
author_facet Silvino, Ana Carolina Rios
Costa, Gabriel Luiz
Araújo, Flávia Carolina Faustino de
Ascher, David Benjamin
Pires, Douglas Eduardo Valente
Fontes, Cor Jesus Fernandes
Carvalho, Luzia Helena
Brito, Cristiana Ferreira Alves de
Sousa, Taís Nóbrega de
author_role author
author2 Costa, Gabriel Luiz
Araújo, Flávia Carolina Faustino de
Ascher, David Benjamin
Pires, Douglas Eduardo Valente
Fontes, Cor Jesus Fernandes
Carvalho, Luzia Helena
Brito, Cristiana Ferreira Alves de
Sousa, Taís Nóbrega de
author2_role author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Silvino, Ana Carolina Rios
Costa, Gabriel Luiz
Araújo, Flávia Carolina Faustino de
Ascher, David Benjamin
Pires, Douglas Eduardo Valente
Fontes, Cor Jesus Fernandes
Carvalho, Luzia Helena
Brito, Cristiana Ferreira Alves de
Sousa, Taís Nóbrega de
dc.subject.other.pt_BR.fl_str_mv Plasmodium vivax
topic Plasmodium vivax
Plasmodium vivax
antimalarial therapy
dc.subject.en.pt_BR.fl_str_mv Plasmodium vivax
antimalarial therapy
description Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Biologia Molecular e Grupo de Pesquisa Imunologia em Malária. Belo Horizonte, MG, Brasil
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2017-07-04T18:53:35Z
dc.date.available.fl_str_mv 2017-07-04T18:53:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/19714
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.eissn.none.fl_str_mv 10.1371/journal.pone.0160172
identifier_str_mv 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.
1932-6203
10.1371/journal.pone.0160172
url https://www.arca.fiocruz.br/handle/icict/19714
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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