TY - JOUR
T1 - Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans
AU - RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics
AU - Rodrigues-Soares, Fernanda
AU - Peñas-Lledó, Eva M.
AU - Tarazona-Santos, Eduardo
AU - Sosa-Macías, Martha
AU - Terán, Enrique
AU - López-López, Marisol
AU - Rodeiro, Idania
AU - Moya, Graciela E.
AU - Calzadilla, Luis R.
AU - Ramírez-Roa, Ronald
AU - Grazina, Manuela
AU - Estévez-Carrizo, Francisco E.
AU - Barrantes, Ramiro
AU - LLerena, Adrián
AU - Tinoco, Catalina Altamirano
AU - Álvárez, Mayra
AU - Borbón, Angélica
AU - Céspedes-Garro, Carolina
AU - Cobaleda, Jesús
AU - de Andrés, Fernando
AU - Delgado, René
AU - Dorado, Pedro
AU - Fariñas, Humberto
AU - Ferreiro, Verónica
AU - Fricke-Galindo, Ingrid
AU - Galaviz-Hernández, Carlos
AU - Garza-Ocañas, Lourdes
AU - Gilman, Robert H.
AU - Hernández, Francisco
AU - Jiménez-Arce, Gerardo
AU - Jung-Cook, Helgi
AU - Lares-Aseff, Ismael
AU - Lazalde-Ramos, Blanca P.
AU - Michelin, Lucas
AU - Monroy-Jaramillo, Nancy
AU - Naranjo, María Eugenia G.
AU - Ortega-Vázquez, Alberto
AU - Ortiz-López, Rocío
AU - Pérez, Bárbaro
AU - Pérez-Páramo, Yadira X.
AU - Remirez, Diadelis
AU - Rojas-Martínez, Augusto
AU - Sarmiento, Alba P.
AU - Scliar, Marilia
AU - Terán, Santiago
AU - Zamudio, Roxana
N1 - Publisher Copyright:
© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85073919824
U2 - 10.1002/cpt.1598
DO - 10.1002/cpt.1598
M3 - Artículo
C2 - 31376146
AN - SCOPUS:85073919824
SN - 0009-9236
VL - 107
SP - 257
EP - 268
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 1
ER -