Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population
Autor(a) principal: | |
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Data de Publicação: | 2016 |
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/10316/108885 https://doi.org/10.15517/rbt.v64i3.20901 |
Resumo: | CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro-Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted. |
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Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican populationCYP2C9CYP2C19CYP2D6Costa RicaAmerindianAfro-Caribbeangenomic ancestryAllelesAmerican Indian or Alaska NativeAsian PeopleBlack PeopleCosta RicaCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9Cytochrome P-450 CYP2D6Gene FrequencyGenotypeHumansReal-Time Polymerase Chain ReactionReference ValuesSelf ReportPolymorphism, GeneticCYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro-Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted.CCG was supported by a fellowship of the University of Costa Rica in the PhD program of the University of Extremadura. The study is part of the Research Program entitled “Genética, Ecología y Salud en los Amerindios de Costa Rica” (N˚742-93-903) and the project N˚ 742-90-416 of the University of Costa Rica. The research was supported by a grant from Junta de Extremadura, Cooperación Extremeña AEXCID 13IA001. ET-S and FRS were supported by the CAPES Agency of the Brazilian Ministry of Education. The project was coordinated in the CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics (RIBEF).Editorial de la Universidad de Costa Rica2016-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108885http://hdl.handle.net/10316/108885https://doi.org/10.15517/rbt.v64i3.20901eng0034-7744Céspedes-Garro, CarolinaRodrigues-Soares, FernandaJiménez-Arce, GerardoNaranjo, María-Eugenia GTarazona-Santos, EduardoFariñas, HumbertoBarrantes, RamiroLlerena, AdriánGrazina, ManuelaCEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics RIBEFainfo: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:RCAAP2023-09-22T09:01:18Zoai:estudogeral.uc.pt:10316/108885Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:07.455127Repositório 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 |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
title |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
spellingShingle |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population Céspedes-Garro, Carolina CYP2C9 CYP2C19 CYP2D6 Costa Rica Amerindian Afro-Caribbean genomic ancestry Alleles American Indian or Alaska Native Asian People Black People Costa Rica Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP2C9 Cytochrome P-450 CYP2D6 Gene Frequency Genotype Humans Real-Time Polymerase Chain Reaction Reference Values Self Report Polymorphism, Genetic |
title_short |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
title_full |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
title_fullStr |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
title_full_unstemmed |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
title_sort |
Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
author |
Céspedes-Garro, Carolina |
author_facet |
Céspedes-Garro, Carolina Rodrigues-Soares, Fernanda Jiménez-Arce, Gerardo Naranjo, María-Eugenia G Tarazona-Santos, Eduardo Fariñas, Humberto Barrantes, Ramiro Llerena, Adrián Grazina, Manuela CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics RIBEFa |
author_role |
author |
author2 |
Rodrigues-Soares, Fernanda Jiménez-Arce, Gerardo Naranjo, María-Eugenia G Tarazona-Santos, Eduardo Fariñas, Humberto Barrantes, Ramiro Llerena, Adrián Grazina, Manuela CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics RIBEFa |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Céspedes-Garro, Carolina Rodrigues-Soares, Fernanda Jiménez-Arce, Gerardo Naranjo, María-Eugenia G Tarazona-Santos, Eduardo Fariñas, Humberto Barrantes, Ramiro Llerena, Adrián Grazina, Manuela CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics RIBEFa |
dc.subject.por.fl_str_mv |
CYP2C9 CYP2C19 CYP2D6 Costa Rica Amerindian Afro-Caribbean genomic ancestry Alleles American Indian or Alaska Native Asian People Black People Costa Rica Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP2C9 Cytochrome P-450 CYP2D6 Gene Frequency Genotype Humans Real-Time Polymerase Chain Reaction Reference Values Self Report Polymorphism, Genetic |
topic |
CYP2C9 CYP2C19 CYP2D6 Costa Rica Amerindian Afro-Caribbean genomic ancestry Alleles American Indian or Alaska Native Asian People Black People Costa Rica Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP2C9 Cytochrome P-450 CYP2D6 Gene Frequency Genotype Humans Real-Time Polymerase Chain Reaction Reference Values Self Report Polymorphism, Genetic |
description |
CYP2C9, CYP2C19 and CYP2D6 metabolize around 40% of drugs and their genes vary across populations. The Costa Rican population has a trihybrid ancestry and its key geographic location turns it into a suitable scenario to evaluate interethnic differences across populations. This study aims to describe the diversity of CYP2C9, CYP2C19 and CYP2D6 polymorphisms in Costa Rican populations in the context of their ancestry. A total of 448 healthy individuals were included in the study: Bribri (n= 47), Cabécar (n= 27), Maleku (n= 16), Guaymí (n= 30), Huetar (n= 48), Chorotega (n= 41), Admixed/Mestizos from the Central Valley/Guanacaste (n= 189), and Afro-Caribbeans (n= 50) from Limón. CYP2C9 (alleles *2, *3, *6) and CYP2C19 (*2, *3, *4, *5, *17) genotypes were determined by Real-Time PCR. African, European and Native American ancestry were inferred using 87 ancestry informative markers. The frequency of the decreased activity allele CYP2C9*2 is lower in the self-reported Amerindian groups compared to the admixed population, and the highest frequencies of CYP2C19*2 (null activity) and the CYP2C19*17 (increased activity) were found in the self-reported Afro-Caribbean population. Moreover, a frequency of 0.7 % CYP2C9 gPMs in the Admixed population and a variable frequency of CYP2C19 gUMs (0.0-32.6 %, more prevalent in Afro-Caribbeans) in Costa Rican populations, was found. Finally, the following alleles were positively correlated with genomic African ancestry and negatively correlated with genomic Native American ancestry: CYP2D6*5 (null activity), CYP2D6*17 (decreased activity), CYP2D6*29 (decreased activity) and CYP2C19*17 (increased activity). No correlation for CYP2C9 polymorphisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-09 |
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/10316/108885 http://hdl.handle.net/10316/108885 https://doi.org/10.15517/rbt.v64i3.20901 |
url |
http://hdl.handle.net/10316/108885 https://doi.org/10.15517/rbt.v64i3.20901 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0034-7744 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Editorial de la Universidad de Costa Rica |
publisher.none.fl_str_mv |
Editorial de la Universidad de Costa Rica |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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