1. Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans
- Author
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Rodrigues-Soares, Fernanda, Peñas-Lledó, Eva, Tarazona, Eduardo, Sosa-Macías, Martha, Terán, Enrique, López-López, Marisol, Rodeiro Guerra, Idania, Moya, Graciela, Calzadilla, Luis R., Ramírez-Roa, Ronald, Grazina, Manuela, Estévez-Carrizo, Francisco E., Barrantes-Reynolds, Ramiro, Llerena, A., Altamirano-Tinoco, Catalina, Alvárez, Mayra, Borbón Orjuela, Angélica Rocío, Céspedes-Garro, Carolina, Cobaleda, Jesús, Andrés, F. de, Delgado, René, Dorado, Pedro, Fariñas, Humberto, Ferreiro, Verónica, Fricke-Galindo, Ingrid, Galaviz-Hernández, Carlos, Garza Ocañas, Lourdes, Gilman, Robert H., Hernández, Francisco, Jíménez-Arce, Gerardo, Jung-Cook, Helgi, Lares-Aseff, Ismael, Lazalde-Ramos, Blanca Patricia, Michelin, Lucas, Monroy-Jaramillo, Nancy, Gómez Naranjo, María Eugenia, Ortega-Vázquez, Alberto, Ortiz-López, Rocío, Pérez, Bárbaro, Pérez-Páramo, Yadira Xitlalli, Remirez, Diadelis, Rojas-Martínez, Augusto, Sarmiento, Alba Piedad, Scliar, Marilia, Terán, Santiago, and Zamudio Zea, Roxana
- Subjects
CYP2C9 ,Latin Americans ,Genetic genealogy ,Black People ,Genomics ,Context (language use) ,CYP2C19 ,Biology ,digestive system ,030226 pharmacology & pharmacy ,White People ,03 medical and health sciences ,0302 clinical medicine ,CYP ,Genetic variation ,Humans ,purl.org/pe-repo/ocde/ford#3.01.05 [https] ,Pharmacology (medical) ,Allele ,skin and connective tissue diseases ,Alleles ,Cytochrome P-450 CYP2C9 ,Ancestry ,Pharmacology ,Genetics ,CYP2D6 ,Racial Groups ,Native American ,Genetic Variation ,Cytochrome P-450 CYP2C19 ,Latin America ,Phenotype ,Cytochrome P-450 CYP2D6 ,Pharmacogenetics ,Genomic Ancestry ,030220 oncology & carcinogenesis ,Indians, North American ,Latin American - Abstract
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.
- Published
- 2019