Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans

We present the distribution of CYP2D6, CYP2C9, and CYP2C19 variants and predicted phenotypes in 33 native and admixed populations from Ibero-America (n > 6,000) in the context of genetic ancestry (n = 3,387). Continental ancestries are the major determinants of frequencies of the increased-activity allele CYP2C19*17 and CYP2C19 gUMs (negatively associated with Native American ancestry), decreased-activity alleles CYP2D6*41 and CYP2C9*2 (positively associated with European ancestry), and decreased-activity alleles CYP2D6*17 and CYP2D6*29 (positively associated with African ancestry). For the rare alleles, CYP2C9*2 and CYPC19*17, European admixture accounts for their presence in Native American populations, but rare alleles CYP2D6*5 (null-activity), CYP2D6-multiplication alleles (increased activity), and CYP2C9*3 (decreased-activity) were present in the pre-Columbian Americas. The study of a broad spectrum of Native American populations from different ethno-linguistic groups show how autochthonous diversity shaped the distribution of pharmaco-alleles and give insights on the prevalence of clinically relevant phenotypes associated with drugs, such as paroxetine, tamoxifen, warfarin, and clopidogrel

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 17

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 17 de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada, de acceso abierto a todas las áreas del conocimiento, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico. Con esta colección, se aspira contribuir con el cultivo, la comprensión, la recopilación y la apropiación social del conocimiento en cuanto a patrimonio intangible de la humanidad, con el propósito de hacer aportes con la transformación de las relaciones socioculturales que sustentan la construcción social de los saberes y su reconocimiento como bien público

Polimorfismos de los citocromos CYP2D6, CYP2C9 y CYP2C19 en la población nicaragüense respecto a otras latinoamericanas

Introducción: Los polimorfismos citocromos P450 pueden conducir a metabolismo lento (ML) o ultrarrápido (MU). Esto puede relacionarse con fallos terapéuticos o efectos adversos en pacientes tratados con sustratos de las enzimas CYP2D6, CYP2C19 y CYP2C9. Objetivos: Determinar en la población nicaragüense mestiza las frecuencias alélicas, genotípicas y fenotipos metabólicos de las enzimas CYP2D6, CYP2C9, CYP2C19 y compararlas con otras poblaciones latinoamericanas. Resultados: CYP2D6. El 6,0 % de los evaluados son metabolizadores lentos (mML) y no se observaron metabolizadores ultrarrápidos (mMU). Según el fenotipo extrapolado del genotipo CYP2D6, 4,0 % son gMLs y 3,0 % son gUMs. Todos los sujetos gMLs también fueron mMLs. El CYP2D6*4 es el más frecuente. CYP2C9. No se observaron sujetos gMLs/gMUs, el CYP2C9*2 es el más frecuente. Las frecuencias de alelos y fenotipos CYP2C9 en nicaragüense son similares a las observadas en otras poblaciones mestizas latinoamericanas. CYP2C19. El 15,3 % fueron gMUs CYP2C19, el CYP2C19*17 es el más frecuente. No hay diferencia entre las frecuencias alélicas y fenotípicas de CYP2D6, CYP2C9 Y CYP2C19 encontradas en la población mestiza de Nicaragua respecto a las observadas en otras poblaciones mestizas latinoamericanas. Conclusiones: Se ha estudiado por primera vez la variabilidad y los polimorfismos de CYP2D6, CYP2C9 y CYP2C19 en la población de Nicaragua, y se ha determinado la existencia de grupos poblacionales con metabolismo diferenciado (Metabolizadores Lentos y Ultrarrápidos). Las frecuencias de estos fenotipos y genotipos metabólicos son similares a otras poblaciones mestizas latinoamericanas.Introduction: Cytochrome P450 genetic polymorphisms are among the main factors responsible for poor (PM) or enhanced metabolic capacity (UM). These variations could lead to therapeutic failures and/or to the occurrence of adverse effects in patients treated with substrates of the enzymes P450, CYP2D6, CYP2C9 and CYP2C19. Objectives: To analyze the frequencies of alleles, genotypes, metabolic phenotypes extrapolated from genotypes of CYP2D6, CYP2C9 and CYP2C19 in Nicaraguans, as well as their potential differences with regard to other Latin American populations. Results: CYP2D6. Metabolic phenotype measured determined that 6 % were poor metabolizers (mPMs), whereas 0 % were ultrarapid metabolizer. According to the CYP2D6 phenotype extrapolated from genotype, 4 % of individuals were gPMs and 3 % gUMs. All the gPMs were also mPMs. The most frequent allele was CYP2D6*4. CYP2C9. No subject was gPMs/gUMs. The more frequent allele was CYP2C9*2. CYP2C19. 15,3 % of Nicaraguan were gUMs; the most frequent allele was CYP2C19*17. The frequencies of alleles, genotypes and phenotypes found in this Nicaraguan Admixed population were similar to the ones observed in other populations from Latin America. Conclusions: This is the first pharmacogenetic study of CYP2D6, CYP2C9 and CYP2C19 polymorphisms in the Nicaraguan population. Additionally, Poor and Ultrarapid metabolizers have been described. The frequencies described for this Nicaraguan Admixed population are similar to other found in other Latin American Admixed populations.La Tesis Doctoral está financiada por la Agencia Extremeña de Cooperación Internacional para el Desarrollo (AEXCID) de la Junta de Extremadura a SIFF (Proyecto MESTIFAR 13IA001); y está coordinada en la Red Iberoamericana de Farmacogenética y Farmacogenómica (RIBEF; www.ribef.com) y el Consorcio CEIBA para el estudio de Farmacogenética de Poblaciones Iberoamericanas. El doctorando ha recibido financiamiento de la Universidad Nacional Autónoma de Nicaragua-León

Polimorfismos de los citocromos CYP2D6, CYP2C9 y CYP2C19 en la población nicaragüense respecto a otras latinoamericanas

Introducción: Los polimorfismos citocromos P450 pueden conducir a metabolismo lento (ML) o ultrarrápido (MU). Esto puede relacionarse con fallos terapéuticos o efectos adversos en pacientes tratados con sustratos de las enzimas CYP2D6, CYP2C19 y CYP2C9. Objetivos: Determinar en la población nicaragüense mestiza las frecuencias alélicas, genotípicas y fenotipos metabólicos de las enzimas CYP2D6, CYP2C9, CYP2C19 y compararlas con otras poblaciones latinoamericanas. Resultados: CYP2D6. El 6,0 % de los evaluados son metabolizadores lentos (mML) y no se observaron metabolizadores ultrarrápidos (mMU). Según el fenotipo extrapolado del genotipo CYP2D6, 4,0 % son gMLs y 3,0 % son gUMs. Todos los sujetos gMLs también fueron mMLs. El CYP2D6*4 es el más frecuente. CYP2C9. No se observaron sujetos gMLs/gMUs, el CYP2C9*2 es el más frecuente. Las frecuencias de alelos y fenotipos CYP2C9 en nicaragüense son similares a las observadas en otras poblaciones mestizas latinoamericanas. CYP2C19. El 15,3 % fueron gMUs CYP2C19, el CYP2C19*17 es el más frecuente. No hay diferencia entre las frecuencias alélicas y fenotípicas de CYP2D6, CYP2C9 Y CYP2C19 encontradas en la población mestiza de Nicaragua respecto a las observadas en otras poblaciones mestizas latinoamericanas. Conclusiones: Se ha estudiado por primera vez la variabilidad y los polimorfismos de CYP2D6, CYP2C9 y CYP2C19 en la población de Nicaragua, y se ha determinado la existencia de grupos poblacionales con metabolismo diferenciado (Metabolizadores Lentos y Ultrarrápidos). Las frecuencias de estos fenotipos y genotipos metabólicos son similares a otras poblaciones mestizas latinoamericanas.Introduction: Cytochrome P450 genetic polymorphisms are among the main factors responsible for poor (PM) or enhanced metabolic capacity (UM). These variations could lead to therapeutic failures and/or to the occurrence of adverse effects in patients treated with substrates of the enzymes P450, CYP2D6, CYP2C9 and CYP2C19. Objectives: To analyze the frequencies of alleles, genotypes, metabolic phenotypes extrapolated from genotypes of CYP2D6, CYP2C9 and CYP2C19 in Nicaraguans, as well as their potential differences with regard to other Latin American populations. Results: CYP2D6. Metabolic phenotype measured determined that 6 % were poor metabolizers (mPMs), whereas 0 % were ultrarapid metabolizer. According to the CYP2D6 phenotype extrapolated from genotype, 4 % of individuals were gPMs and 3 % gUMs. All the gPMs were also mPMs. The most frequent allele was CYP2D6*4. CYP2C9. No subject was gPMs/gUMs. The more frequent allele was CYP2C9*2. CYP2C19. 15,3 % of Nicaraguan were gUMs; the most frequent allele was CYP2C19*17. The frequencies of alleles, genotypes and phenotypes found in this Nicaraguan Admixed population were similar to the ones observed in other populations from Latin America. Conclusions: This is the first pharmacogenetic study of CYP2D6, CYP2C9 and CYP2C19 polymorphisms in the Nicaraguan population. Additionally, Poor and Ultrarapid metabolizers have been described. The frequencies described for this Nicaraguan Admixed population are similar to other found in other Latin American Admixed populations.La Tesis Doctoral está financiada por la Agencia Extremeña de Cooperación Internacional para el Desarrollo (AEXCID) de la Junta de Extremadura a SIFF (Proyecto MESTIFAR 13IA001); y está coordinada en la Red Iberoamericana de Farmacogenética y Farmacogenómica (RIBEF; www.ribef.com) y el Consorcio CEIBA para el estudio de Farmacogenética de Poblaciones Iberoamericanas. El doctorando ha recibido financiamiento de la Universidad Nacional Autónoma de Nicaragua-León

Interethnic variability in CYP2D6, CYP2C9, and CYP2C19 genes and predicted drug metabolism phenotypes among 6060 Ibero- and native americans: RIBEF-CEIBA Consortium Report on population pharmacogenomics

Abstarct Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their "predicted drug metabolism phenotypes" across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews. Moreover, Native Americans were grouped into North-, Central-, and South Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic variants, and grouped as genotype-predicted poor or ultrarapid metabolizer phenotypes (gPMs and gUMs, respectively). Native Americans showed differences from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19. Native Americans had higher frequencies of wild-type alleles for all genes, and lower frequency of CYP2D6*41, CYP2C9*2, and CYP2C19*17 (p < 0.05). Native Americans also showed less CYP2C19 gUMs than the rest of the population sample. In addition, differences within Native Americans (mostly North vs. South) were also found. The interethnic differences described supports the need for population-specific personalized and precision medicine programs for Native Americans. To the best of our knowledge, this is the largest study carried out in Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9, and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field of global health and warrants further research and education

Interethnic Variability in CYP2D6, CYP2C9, and CYP2C19 Genes and Predicted Drug Metabolism Phenotypes Among 6060 Ibero- and Native Americans: RIBEF-CEIBA Consortium Report on Population Pharmacogenomics

Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their "predicted drug metabolism phenotypes" across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews. Moreover, Native Americans were grouped into North-, Central-, and South Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic variants, and grouped as genotype-predicted poor or ultrarapid metabolizer phenotypes (gPMs and gUMs, respectively). Native Americans showed differences from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19. Native Americans had higher frequencies of wild-type alleles for all genes, and lower frequency of CYP2D6*41, CYP2C9*2, and CYP2C19*17 (p < 0.05). Native Americans also showed less CYP2C19 gUMs than the rest of the population sample. In addition, differences within Native Americans (mostly North vs. South) were also found. The interethnic differences described supports the need for population-specific personalized and precision medicine programs for Native Americans. To the best of our knowledge, this is the largest study carried out in Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9, and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field of global health and warrants further research and education

Volumen 18 Número 1

Revista seriada del Instituto Humboldt en asocio con el Invemar, el Instituto de Ciencias Naturales (ICN) y el Missouri Botanical Garden, como una estrategia para ampliar la base del conocimiento de uno de los países con mayor diversidad biológica del mundo. Inicia como una publicación de listados de especies pero en 2005 amplía su espectro temático hacia la sistemática y la biogeografía. En 2010, a propósito del Año Internacional de la Biodiversidad y en pro del conocimiento, la conservación y el uso sostenible de la biodiversidad, se abre a un público más amplio, considerando trabajos inéditos de investigación sobre botánica, zoología, ecología, biología, limnología, pesquerías, conservación, manejo de recursos y uso de la biodiversidad, con buena aceptación por parte de la comunidad científica y académica. En 2013, en asocio con el SiB Colombia y con el apoyo de la GBIF, se institucionaliza la inclusión de Artículos de Datos (Data Papers) en Biota Colombiana