The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial

Autores
León Cachón, Rafael B. R.; Bamford, Aileen Diane; Meester, Irene; Barrera Saldaña, Hugo Alberto; Gómez Silva, Magdalena; Garcia Bustos, Maria Fernanda
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Atorvastatin (ATV) is a blood cholesterol-lowering drug used to prevent cardiovascular events, the leading cause of death worldwide. As pharmacokinetics, metabolism and response vary among individuals, we wanted to determine the most reliable metabolic ATV phenotypes and identify novel and preponderant genetic markers that affect ATV plasma levels. A controlled, randomized, crossover, single-blind, three-treatment, three-period, and six-sequence clinical study of ATV (single 80-mg oral dose) was conducted among 60 healthy Mexican men. ATV plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed by real-time PCR with TaqMan probes. Four ATV metabolizer phenotypes were found: slow, intermediate, normal and fast. Six gene polymorphisms, SLCO1B1-rs4149056, ABCB1-rs1045642, CYP2D6-rs1135840, CYP2B6-rs3745274, NAT2-rs1208, and COMT- rs4680, had a significant effect on ATV pharmacokinetics (P < 0.05). The polymorphisms in SLCO1B1 and ABCB1 seemed to have a greater effect and were especially important for the shift from an intermediate to a normal metabolizer. This is the first study that demonstrates how the interaction of genetic variants affect metabolic phenotyping and improves understanding of how SLCO1B1 and ABCB1 variants that affect statin metabolism may partially explain the variability in drug response. Notwithstanding, the influence of other genetic and non-genetic factors is not ruled out.
Fil: León Cachón, Rafael B. R.. Universidad de Monterrey.; México
Fil: Bamford, Aileen Diane. Universidad de Monterrey.; México
Fil: Meester, Irene. Universidad de Monterrey.; México
Fil: Barrera Saldaña, Hugo Alberto. Vitagenesis S.A.; México. Innbiogem S.C.; México
Fil: Gómez Silva, Magdalena. Universidad Autonoma de Nuevo Leon.; México
Fil: Garcia Bustos, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
Materia
ATORVASTATIN METABOLISM
ATORVASTATIN PHARMACOGENETICS
MEXICAN POPULATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/129200
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trialLeón Cachón, Rafael B. R.Bamford, Aileen DianeMeester, IreneBarrera Saldaña, Hugo AlbertoGómez Silva, MagdalenaGarcia Bustos, Maria FernandaATORVASTATIN METABOLISMATORVASTATIN PHARMACOGENETICSMEXICAN POPULATIONhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Atorvastatin (ATV) is a blood cholesterol-lowering drug used to prevent cardiovascular events, the leading cause of death worldwide. As pharmacokinetics, metabolism and response vary among individuals, we wanted to determine the most reliable metabolic ATV phenotypes and identify novel and preponderant genetic markers that affect ATV plasma levels. A controlled, randomized, crossover, single-blind, three-treatment, three-period, and six-sequence clinical study of ATV (single 80-mg oral dose) was conducted among 60 healthy Mexican men. ATV plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed by real-time PCR with TaqMan probes. Four ATV metabolizer phenotypes were found: slow, intermediate, normal and fast. Six gene polymorphisms, SLCO1B1-rs4149056, ABCB1-rs1045642, CYP2D6-rs1135840, CYP2B6-rs3745274, NAT2-rs1208, and COMT- rs4680, had a significant effect on ATV pharmacokinetics (P < 0.05). The polymorphisms in SLCO1B1 and ABCB1 seemed to have a greater effect and were especially important for the shift from an intermediate to a normal metabolizer. This is the first study that demonstrates how the interaction of genetic variants affect metabolic phenotyping and improves understanding of how SLCO1B1 and ABCB1 variants that affect statin metabolism may partially explain the variability in drug response. Notwithstanding, the influence of other genetic and non-genetic factors is not ruled out.Fil: León Cachón, Rafael B. R.. Universidad de Monterrey.; MéxicoFil: Bamford, Aileen Diane. Universidad de Monterrey.; MéxicoFil: Meester, Irene. Universidad de Monterrey.; MéxicoFil: Barrera Saldaña, Hugo Alberto. Vitagenesis S.A.; México. Innbiogem S.C.; MéxicoFil: Gómez Silva, Magdalena. Universidad Autonoma de Nuevo Leon.; MéxicoFil: Garcia Bustos, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaNature Research2020-06-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/129200León Cachón, Rafael B. R.; Bamford, Aileen Diane; Meester, Irene; Barrera Saldaña, Hugo Alberto; Gómez Silva, Magdalena; et al.; The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial; Nature Research; Scientific Reports; 10; 1; 1-6-2020; 1-112045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-020-65843-yinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-65843-yinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:56Zoai:ri.conicet.gov.ar:11336/129200instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:56.457CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
title The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
spellingShingle The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
León Cachón, Rafael B. R.
ATORVASTATIN METABOLISM
ATORVASTATIN PHARMACOGENETICS
MEXICAN POPULATION
title_short The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
title_full The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
title_fullStr The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
title_full_unstemmed The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
title_sort The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial
dc.creator.none.fl_str_mv León Cachón, Rafael B. R.
Bamford, Aileen Diane
Meester, Irene
Barrera Saldaña, Hugo Alberto
Gómez Silva, Magdalena
Garcia Bustos, Maria Fernanda
author León Cachón, Rafael B. R.
author_facet León Cachón, Rafael B. R.
Bamford, Aileen Diane
Meester, Irene
Barrera Saldaña, Hugo Alberto
Gómez Silva, Magdalena
Garcia Bustos, Maria Fernanda
author_role author
author2 Bamford, Aileen Diane
Meester, Irene
Barrera Saldaña, Hugo Alberto
Gómez Silva, Magdalena
Garcia Bustos, Maria Fernanda
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv ATORVASTATIN METABOLISM
ATORVASTATIN PHARMACOGENETICS
MEXICAN POPULATION
topic ATORVASTATIN METABOLISM
ATORVASTATIN PHARMACOGENETICS
MEXICAN POPULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Atorvastatin (ATV) is a blood cholesterol-lowering drug used to prevent cardiovascular events, the leading cause of death worldwide. As pharmacokinetics, metabolism and response vary among individuals, we wanted to determine the most reliable metabolic ATV phenotypes and identify novel and preponderant genetic markers that affect ATV plasma levels. A controlled, randomized, crossover, single-blind, three-treatment, three-period, and six-sequence clinical study of ATV (single 80-mg oral dose) was conducted among 60 healthy Mexican men. ATV plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed by real-time PCR with TaqMan probes. Four ATV metabolizer phenotypes were found: slow, intermediate, normal and fast. Six gene polymorphisms, SLCO1B1-rs4149056, ABCB1-rs1045642, CYP2D6-rs1135840, CYP2B6-rs3745274, NAT2-rs1208, and COMT- rs4680, had a significant effect on ATV pharmacokinetics (P < 0.05). The polymorphisms in SLCO1B1 and ABCB1 seemed to have a greater effect and were especially important for the shift from an intermediate to a normal metabolizer. This is the first study that demonstrates how the interaction of genetic variants affect metabolic phenotyping and improves understanding of how SLCO1B1 and ABCB1 variants that affect statin metabolism may partially explain the variability in drug response. Notwithstanding, the influence of other genetic and non-genetic factors is not ruled out.
Fil: León Cachón, Rafael B. R.. Universidad de Monterrey.; México
Fil: Bamford, Aileen Diane. Universidad de Monterrey.; México
Fil: Meester, Irene. Universidad de Monterrey.; México
Fil: Barrera Saldaña, Hugo Alberto. Vitagenesis S.A.; México. Innbiogem S.C.; México
Fil: Gómez Silva, Magdalena. Universidad Autonoma de Nuevo Leon.; México
Fil: Garcia Bustos, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina
description Atorvastatin (ATV) is a blood cholesterol-lowering drug used to prevent cardiovascular events, the leading cause of death worldwide. As pharmacokinetics, metabolism and response vary among individuals, we wanted to determine the most reliable metabolic ATV phenotypes and identify novel and preponderant genetic markers that affect ATV plasma levels. A controlled, randomized, crossover, single-blind, three-treatment, three-period, and six-sequence clinical study of ATV (single 80-mg oral dose) was conducted among 60 healthy Mexican men. ATV plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed by real-time PCR with TaqMan probes. Four ATV metabolizer phenotypes were found: slow, intermediate, normal and fast. Six gene polymorphisms, SLCO1B1-rs4149056, ABCB1-rs1045642, CYP2D6-rs1135840, CYP2B6-rs3745274, NAT2-rs1208, and COMT- rs4680, had a significant effect on ATV pharmacokinetics (P < 0.05). The polymorphisms in SLCO1B1 and ABCB1 seemed to have a greater effect and were especially important for the shift from an intermediate to a normal metabolizer. This is the first study that demonstrates how the interaction of genetic variants affect metabolic phenotyping and improves understanding of how SLCO1B1 and ABCB1 variants that affect statin metabolism may partially explain the variability in drug response. Notwithstanding, the influence of other genetic and non-genetic factors is not ruled out.
publishDate 2020
dc.date.none.fl_str_mv 2020-06-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/129200
León Cachón, Rafael B. R.; Bamford, Aileen Diane; Meester, Irene; Barrera Saldaña, Hugo Alberto; Gómez Silva, Magdalena; et al.; The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial; Nature Research; Scientific Reports; 10; 1; 1-6-2020; 1-11
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/129200
identifier_str_mv León Cachón, Rafael B. R.; Bamford, Aileen Diane; Meester, Irene; Barrera Saldaña, Hugo Alberto; Gómez Silva, Magdalena; et al.; The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial; Nature Research; Scientific Reports; 10; 1; 1-6-2020; 1-11
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41598-020-65843-y
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-020-65843-y
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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