Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans. Issue 1 (7th October 2019)

• Record Type: Journal Article
• Authors: Rodrigues‐Soares, Fernanda; Peñas‐Lledó, Eva M.; Tarazona‐Santos, Eduardo; Sosa‐Macías, Martha; Terán, Enrique; López‐López, Marisol; Rodeiro, Idania; Moya, Graciela E.; Calzadilla, Luis R.; Ramírez‐Roa, Ronald; Grazina, Manuela; Estévez‐Carrizo, Francisco E.; Barrantes, Ramiro; LLerena, Adrián
• Other Names: Tinoco Catalina Altamirano investigator.; Álvárez Mayra investigator.; Borbón Angélica investigator.; Céspedes‐Garro Carolina investigator.; Cobaleda Jesús investigator.; de Andrés Fernando investigator.; Delgado René investigator.; Dorado Pedro investigator.; Fariñas Humberto investigator.; Ferreiro Verónica investigator.; Fricke‐Galindo Ingrid investigator.; Galaviz‐Hernández Carlos investigator.; Garza‐Ocañas Lourdes investigator.; Gilman Robert H. investigator.; Hernández Francisco investigator.; Jiménez‐Arce Gerardo investigator.; Jung‐Cook Helgi investigator.; Lares‐Aseff Ismael investigator.; Lazalde‐Ramos Blanca P. investigator.; Michelin Lucas investigator.; Monroy‐Jaramillo Nancy investigator.; Naranjo María Eugenia G. investigator.; Ortega‐Vázquez Alberto investigator.; Ortiz‐López Rocío investigator.; Pérez Bárbaro investigator.; Pérez‐Páramo Yadira X. investigator.; Remirez Diadelis investigator.; Rojas‐Martínez Augusto investigator.; Sarmiento Alba P. investigator.; Scliar Marilia investigator.; Terán Santiago investigator.; Zamudio Roxana investigator.;
• Is Part Of: Clinical pharmacology & therapeutics. Volume 107:Issue 1(2020)
• Page Start: 257
• Page End: 268
• Publication Date: 2019-10-07
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1002/cpt.1598
• Languages: English
• ISSNs: 0009-9236

Abstract

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.