High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/62287 |
Resumo: | Voriconazole is a triazole antifungal agent recommended as primary treatment for invasive aspergillosis, as well as some other mold infections. However, it presents some pharmacokinetic singularities that lead to a great variability intra- and interindividually, nonlinear pharmacokinetics, and a narrow therapeutic range. Most experts have recommended tracing the levels of voriconazole in patients when receiving treatment. This azole is metabolized through the hepatic enzyme complex cytochrome P450 (CYPP450), with the isoenzyme CYP2C19 being principally involved. Allelic variations (polymorphisms) of the gene that encodes this enzyme are known to contribute to variability in voriconazole exposure. Three different allelic variants, CYP2C19*17, CYP2C19*2, and CYP2C19*3, could explain most of the phenotypes related to the voriconazole metabolism and some of its pharmacokinetic singularities. We designed a rapid molecular method based on high-resolution melting to characterize these polymorphisms in a total of 142 samples, avoiding sequencing. Three PCRs were designed with similar cycling conditions to run simultaneously. The results showed that our method represents a fast, accurate, and inexpensive means to study these variants related to voriconazole metabolism. In clinical practice, this could offer a useful tool to individually optimize therapy and reduce expenses in patients with fungal infections. |
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High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectivenessCYP2C19High-resolution meltingVoriconazolePharmacogenomicsPolymorphismsCiências Médicas::Medicina BásicaScience & TechnologyVoriconazole is a triazole antifungal agent recommended as primary treatment for invasive aspergillosis, as well as some other mold infections. However, it presents some pharmacokinetic singularities that lead to a great variability intra- and interindividually, nonlinear pharmacokinetics, and a narrow therapeutic range. Most experts have recommended tracing the levels of voriconazole in patients when receiving treatment. This azole is metabolized through the hepatic enzyme complex cytochrome P450 (CYPP450), with the isoenzyme CYP2C19 being principally involved. Allelic variations (polymorphisms) of the gene that encodes this enzyme are known to contribute to variability in voriconazole exposure. Three different allelic variants, CYP2C19*17, CYP2C19*2, and CYP2C19*3, could explain most of the phenotypes related to the voriconazole metabolism and some of its pharmacokinetic singularities. We designed a rapid molecular method based on high-resolution melting to characterize these polymorphisms in a total of 142 samples, avoiding sequencing. Three PCRs were designed with similar cycling conditions to run simultaneously. The results showed that our method represents a fast, accurate, and inexpensive means to study these variants related to voriconazole metabolism. In clinical practice, this could offer a useful tool to individually optimize therapy and reduce expenses in patients with fungal infections.National Institute of Health Carlos III (AES13PI13/01817Research Project MPY 1367/13). L.B.-M. has a contract supported by theMinisterio de Ciencia e Innovación, Instituto de Salud Carlos III, cofinanced by the EuropeanDevelopment Regional Fund (EDRF) “A Way to Achieve Europe” and the SpanishNetwork for the Research in Infectious Diseases (REIPI; RD12/0015/0015). B.M.-R. is astudent in the Master’s Program entitled “Microbiología Aplicada a la Salud Pública eInvestigación en Enfermedades Infecciosas,” Alcalá de Henares University, Madrid,Spain. A.C. and C.C. were supported by the Northern Portugal Regional OperationalProgram (NORTE 2020) under the Portugal 2020 Partnership Agreement through theEuropean Regional Development Fund (FEDER; NORTE-01-0145-FEDER-000013) and theFundação Para a Ciência e Tecnologia (FCT; IF/00735/2014 [A.C.] and SFRH/BPD/96176/2013 [C.C.]).American Society for Microbiology (ASM)Universidade do MinhoBernal-Martínez, L.Alcazar Fuoli, L.Miguel-Revilla, B.Carvalho, A.Cuétara Garcia, M. S.Garcia-Rodriguez, J.Cunha, C.Gómez-García de la Pedrosa, E.Gomez-Lopez, A.2019-062019-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/62287engBernal-Martínez, L., Fuoli, L. A., Miguel-Revilla, B., Carvalho, A., Garcia, M. C., Garcia-Rodriguez, J., ... & Gomez-Lopez, A. (2019). High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrobial agents and chemotherapy, 63(6), e02399-18.0066-48041098-659610.1128/AAC.02399-1830910893https://aac.asm.org/content/63/6/e02399-18.abstractinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:06:15Zoai:repositorium.sdum.uminho.pt:1822/62287Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:56:52.212422Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
title |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
spellingShingle |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness Bernal-Martínez, L. CYP2C19 High-resolution melting Voriconazole Pharmacogenomics Polymorphisms Ciências Médicas::Medicina Básica Science & Technology |
title_short |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
title_full |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
title_fullStr |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
title_full_unstemmed |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
title_sort |
High-resolution melting assay for genotyping variants of the CYP2C19 enzyme and predicting voriconazole effectiveness |
author |
Bernal-Martínez, L. |
author_facet |
Bernal-Martínez, L. Alcazar Fuoli, L. Miguel-Revilla, B. Carvalho, A. Cuétara Garcia, M. S. Garcia-Rodriguez, J. Cunha, C. Gómez-García de la Pedrosa, E. Gomez-Lopez, A. |
author_role |
author |
author2 |
Alcazar Fuoli, L. Miguel-Revilla, B. Carvalho, A. Cuétara Garcia, M. S. Garcia-Rodriguez, J. Cunha, C. Gómez-García de la Pedrosa, E. Gomez-Lopez, A. |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Bernal-Martínez, L. Alcazar Fuoli, L. Miguel-Revilla, B. Carvalho, A. Cuétara Garcia, M. S. Garcia-Rodriguez, J. Cunha, C. Gómez-García de la Pedrosa, E. Gomez-Lopez, A. |
dc.subject.por.fl_str_mv |
CYP2C19 High-resolution melting Voriconazole Pharmacogenomics Polymorphisms Ciências Médicas::Medicina Básica Science & Technology |
topic |
CYP2C19 High-resolution melting Voriconazole Pharmacogenomics Polymorphisms Ciências Médicas::Medicina Básica Science & Technology |
description |
Voriconazole is a triazole antifungal agent recommended as primary treatment for invasive aspergillosis, as well as some other mold infections. However, it presents some pharmacokinetic singularities that lead to a great variability intra- and interindividually, nonlinear pharmacokinetics, and a narrow therapeutic range. Most experts have recommended tracing the levels of voriconazole in patients when receiving treatment. This azole is metabolized through the hepatic enzyme complex cytochrome P450 (CYPP450), with the isoenzyme CYP2C19 being principally involved. Allelic variations (polymorphisms) of the gene that encodes this enzyme are known to contribute to variability in voriconazole exposure. Three different allelic variants, CYP2C19*17, CYP2C19*2, and CYP2C19*3, could explain most of the phenotypes related to the voriconazole metabolism and some of its pharmacokinetic singularities. We designed a rapid molecular method based on high-resolution melting to characterize these polymorphisms in a total of 142 samples, avoiding sequencing. Three PCRs were designed with similar cycling conditions to run simultaneously. The results showed that our method represents a fast, accurate, and inexpensive means to study these variants related to voriconazole metabolism. In clinical practice, this could offer a useful tool to individually optimize therapy and reduce expenses in patients with fungal infections. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-06 2019-06-01T00:00:00Z |
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.uri.fl_str_mv |
http://hdl.handle.net/1822/62287 |
url |
http://hdl.handle.net/1822/62287 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bernal-Martínez, L., Fuoli, L. A., Miguel-Revilla, B., Carvalho, A., Garcia, M. C., Garcia-Rodriguez, J., ... & Gomez-Lopez, A. (2019). High-Resolution Melting Assay for Genotyping Variants of the CYP2C19 Enzyme and Predicting Voriconazole Effectiveness. Antimicrobial agents and chemotherapy, 63(6), e02399-18. 0066-4804 1098-6596 10.1128/AAC.02399-18 30910893 https://aac.asm.org/content/63/6/e02399-18.abstract |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Society for Microbiology (ASM) |
publisher.none.fl_str_mv |
American Society for Microbiology (ASM) |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132356540366848 |