Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/59609 |
Resumo: | Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism. |
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Almeida, Anne C. G.Puça, Maria C. B.Figueiredo, Erick F. G.Barbosa, Laila R.Salazar, Yanka E. A. R.Silva, Emanuelle L.Brito, Marcelo A. M.Siqueira, André M.Vieira, José L. F.Lacerda, Marcus V. G.Monteiro, Wuelton M.Melo, Gisely C.2023-07-15T16:19:08Z2023-07-15T16:19:08Z2020ALMEIDA, Anne C. G. et al. Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax. Antimicrobial Agents and Chemotherapy, v. 64, n. 7, p. 1-11 Jun. 2020.1098-6596https://www.arca.fiocruz.br/handle/icict/5960910.1128/AAC.02125-190066-4804Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Pará. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto Leônidas & Maria Deane. Manaus, AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Instituto de Pesquisa Clínica Carlos Borborema. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Programa de Pós-graduação em Medicina Tropical. Manaus, AM, Brasil.engAmerican Society for Microbiologyhttps://www.arca.fiocruz.br/handle/icict/43101Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivaxinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCYP450Plasmodium vivaxChloroquineEarly recurrenceMalariainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/59609/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALve_Anne_Almeida_etal_INI_ILMD_2020_ARTIGO_FINAL.pdfve_Anne_Almeida_etal_INI_ILMD_2020_ARTIGO_FINAL.pdfapplication/pdf883196https://www.arca.fiocruz.br/bitstream/icict/59609/2/ve_Anne_Almeida_etal_INI_ILMD_2020_ARTIGO_FINAL.pdfad60a68cef64c44062f3180aa6fd82d1MD52icict/596092023-07-15 19:24:36.062oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-07-15T22:24:36Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.en_US.fl_str_mv |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
title |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
spellingShingle |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax Almeida, Anne C. G. CYP450 Plasmodium vivax Chloroquine Early recurrence Malaria |
title_short |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
title_full |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
title_fullStr |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
title_full_unstemmed |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
title_sort |
Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax |
author |
Almeida, Anne C. G. |
author_facet |
Almeida, Anne C. G. Puça, Maria C. B. Figueiredo, Erick F. G. Barbosa, Laila R. Salazar, Yanka E. A. R. Silva, Emanuelle L. Brito, Marcelo A. M. Siqueira, André M. Vieira, José L. F. Lacerda, Marcus V. G. Monteiro, Wuelton M. Melo, Gisely C. |
author_role |
author |
author2 |
Puça, Maria C. B. Figueiredo, Erick F. G. Barbosa, Laila R. Salazar, Yanka E. A. R. Silva, Emanuelle L. Brito, Marcelo A. M. Siqueira, André M. Vieira, José L. F. Lacerda, Marcus V. G. Monteiro, Wuelton M. Melo, Gisely C. |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Almeida, Anne C. G. Puça, Maria C. B. Figueiredo, Erick F. G. Barbosa, Laila R. Salazar, Yanka E. A. R. Silva, Emanuelle L. Brito, Marcelo A. M. Siqueira, André M. Vieira, José L. F. Lacerda, Marcus V. G. Monteiro, Wuelton M. Melo, Gisely C. |
dc.subject.en.none.fl_str_mv |
CYP450 Plasmodium vivax Chloroquine Early recurrence Malaria |
topic |
CYP450 Plasmodium vivax Chloroquine Early recurrence Malaria |
description |
Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020 |
dc.date.accessioned.fl_str_mv |
2023-07-15T16:19:08Z |
dc.date.available.fl_str_mv |
2023-07-15T16:19:08Z |
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 |
ALMEIDA, Anne C. G. et al. Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax. Antimicrobial Agents and Chemotherapy, v. 64, n. 7, p. 1-11 Jun. 2020. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/59609 |
dc.identifier.issn.en_US.fl_str_mv |
1098-6596 |
dc.identifier.doi.none.fl_str_mv |
10.1128/AAC.02125-19 |
dc.identifier.eissn.none.fl_str_mv |
0066-4804 |
identifier_str_mv |
ALMEIDA, Anne C. G. et al. Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax. Antimicrobial Agents and Chemotherapy, v. 64, n. 7, p. 1-11 Jun. 2020. 1098-6596 10.1128/AAC.02125-19 0066-4804 |
url |
https://www.arca.fiocruz.br/handle/icict/59609 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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https://www.arca.fiocruz.br/handle/icict/43101 |
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openAccess |
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American Society for Microbiology |
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American Society for Microbiology |
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