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 - Funding Information:
This word was supported by Junta Extremadura-AEXCID (PATLI, 18IA003) to the Ibero-American Society of Pharmacogenetics and Pharmacogenomics (SIFF) and to the RIBEF Network (www.redribef.com). This work also received support from the Brazilian National Research Council (CNPq), Coordination for the Improvement of Higher Education Personnel – Brazilian Ministry of Education (CAPES), and Pró-Reitoria de Pesquisa-Universidade Federal de Minas Gerais. F.R.-S. received a CAPES-PDSE fellowship to spend a year at the University of Extremadura, and E.T. received a Collaborative Grant 2014 from Universidad San Francisco de Quito.
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.
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U2 - 10.1002/cpt.1598
DO - 10.1002/cpt.1598
M3 - Article
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 -