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

Rodrigues-Soares F.; Peñas-Lledó E.M.; Tarazona-Santos E.; Sosa-Macías M.; Terán E.; López-López M.; Rodeiro I.; Moya G.E.; Calzadilla L.R.; Ramírez-Roa R.; Grazina M.; Estévez-Carrizo F.E.; Barrantes R.; LLerena A.; Tinoco C.A.; Álvárez M.; Borbón A.; Céspedes-Garro C.; Cobaleda J.; de Andrés F.; Delgado R.; Dorado P.; Fariñas H.; Ferreiro V.; Fricke-Galindo I.; Galaviz-Hernández C.; Garza-Ocañas L.; Gilman R.H.; Hernández F.; Jiménez-Arce G.; Jung-Cook H.; Lares-Aseff I.; Lazalde-Ramos B.P.; Michelin L.; Monroy-Jaramillo N.; Naranjo M.E.G.; Ortega-Vázquez A.; Ortiz-López R.; Pérez B.; Pérez-Páramo Y.X.; Remirez D.; Rojas-Martínez A.; Sarmiento A.P.; Scliar M.; Terán S.; Zamudio R. · Clinical Pharmacology and Therapeutics (2020) · DOI: 10.1002/cpt.1598

Resumen

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.

Instituciones: Universidad Peruana Cayetano Heredia