Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population
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| Formato: | Artículo científico |
| Lenguaje: | en |
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Universidad de Costa Rica
2016
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| _version_ | 1876445025864253440 |
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| author | Carolina Céspedes-Garro |
| author_facet | Carolina Céspedes-Garro |
| contents | Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population Carolina Céspedes-Garro Fernanda Rodrigues-Soares Gerardo Jiménez-Arce María-Eugenia G. Naranjo Eduardo Tarazona-Santos Humberto Fariñas Ramiro Barrantes Adrián Llerena CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics RIBEF Biología Afro CYP2C9 CYP2D6 CYP2C19 Caribbean 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 Lim ó n. 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 polymor - phisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted. 2016 artículo científico 0034-7744 https://www.redalyc.org/articulo.oa?id=44946472012 https://www.redalyc.org/journal/449/44946472012/ https://www.redalyc.org/journal/449/44946472012/html/ https://www.redalyc.org/journal/449/44946472012/44946472012.epub https://www.redalyc.org/journal/449/44946472012/movil en http://www.redalyc.org/revista.oa?id=449 Revista de Biología Tropical application/pdf Universidad de Costa Rica Revista de Biología Tropical (Costa Rica) Num.3 Vol.64 |
| format | Artículo científico |
| id | redalyc_44946472012 |
| institution | Redalyc |
| language | en |
| publishDate | 2016 |
| publisher | Universidad de Costa Rica |
| spellingShingle | Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population Carolina Céspedes-Garro Biología Afro CYP2C9 CYP2D6 CYP2C19 Caribbean Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population Carolina Céspedes-Garro Fernanda Rodrigues-Soares Gerardo Jiménez-Arce María-Eugenia G. Naranjo Eduardo Tarazona-Santos Humberto Fariñas Ramiro Barrantes Adrián Llerena CEIBA.FP Consortium of the Ibero-American Network of Pharmacogenetics & Pharmacogenomics RIBEF Biología Afro CYP2C9 CYP2D6 CYP2C19 Caribbean 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 Lim ó n. 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 polymor - phisms and genomic ancestry was found. Further studies assessing the CYP2C9 and CYP2C19 sequence in these populations, preferentially by sequencing these genes, are warranted. 2016 artículo científico 0034-7744 https://www.redalyc.org/articulo.oa?id=44946472012 https://www.redalyc.org/journal/449/44946472012/ https://www.redalyc.org/journal/449/44946472012/html/ https://www.redalyc.org/journal/449/44946472012/44946472012.epub https://www.redalyc.org/journal/449/44946472012/movil en http://www.redalyc.org/revista.oa?id=449 Revista de Biología Tropical application/pdf Universidad de Costa Rica Revista de Biología Tropical (Costa Rica) Num.3 Vol.64 |
| title | Relevance of the ancestry for the variability of the Drug-Metabolizing Enzymes CYP2C9, CYP2C19 and CYP2D6 polymorphisms in a multiethnic Costa Rican population |
| topic | Biología Afro CYP2C9 CYP2D6 CYP2C19 Caribbean |
| url | https://www.redalyc.org/articulo.oa?id=44946472012 https://www.redalyc.org/journal/449/44946472012/ https://www.redalyc.org/journal/449/44946472012/html/ https://www.redalyc.org/journal/449/44946472012/44946472012.epub https://www.redalyc.org/journal/449/44946472012/movil |