Interethnic variability in CYP2D6, CYP2C9, and CYP2C19 genes and predicted drug metabolism phenotypes among 6060 ibero-and native Americans: RIBEF-CEIBA consortium report on population pharmacogenomics

María Eugenia G. Naranjo, Fernanda Rodrigues-Soares, Eva M. Peñas-Lledó, Eduardo Tarazona-Santos, Humberto Fariñas, Idania Rodeiro, Enrique Terán, Manuela Grazina, Graciela E. Moya, Marisol López-López, Alba P. Sarmiento, Luis R. Calzadilla, Ronald Ramírez-Roa, Rocío Ortiz-López, Francisco E. Estévez-Carrizo, Martha Sosa-Macías, Ramiro Barrantes, Adrián L. Lerena, Verónica Fcrreiro, Marilia O. ScliarMateus H. Gouveia, Angelica Borbon, Gerardo Jiménez-Arce, Carolina Céspedes-Garro, Mayra Álvárez, René Delgado, Diadelis Remirez, Bárbaro Pérez, Francisco Hernández, Santiago Terán, Augusto Rojas-Martinez, Lourdes Garza-Ocañas, Yadira X. Pérez-Páramo, Alberto Ortega-Vázquez, Nancy Monroy-Jaramillo, Helgi Jung-Cook, Ingrid Fricke-Galindo, Carlos Galaviz-Hernández, Ismael Lares-Aseff, Blanca P. Lazalde-Ramos, Catalina Altamirano Tinoco, Roxana Zamudio, Robert H. Gilman, Jesús Cobaleda, Fernando de Andrés, Pedro Dorado

Research output: Contribution to journalArticlepeer-review

Abstract

Pharmacogenetic variation in Latin Americans is understudied, which sets a barrier for the goal of global precision medicine. The RIBEF-CEIBA Network Consortium was established to characterize interindividual and between population variations in CYP2D6, CYP2C9, and CYP2C19 drug metabolizing enzyme genotypes, which were subsequently utilized to catalog their "predicted drug metabolism phenotypes" across Native American and Ibero American populations. Importantly, we report in this study, a total of 6060 healthy individuals from Ibero-America who were classified according to their self-reported ancestry: 1395 Native Americans, 2571 Admixed Latin Americans, 96 Afro-Latin Americans, 287 white Latin Americans (from Cuba), 1537 Iberians, and 174 Argentinean Ashkenazi Jews. Moreover, Native Americans were grouped into North-, Central-, and South Amerindians (from Mexico, Costa Rica, and Peru, respectively). All subjects were studied for the most common and functional CYP2D6, CYP2C9, and CYP2C19 allelic variants, and grouped as genotype-predicted poor or ultrarapid metabolizer phenotypes (gPMs and gUMs, respectively). Native Americans showed differences from each ethnic group in at least two alleles of CYP2D6, CYP2C9, and CYP2C19. Native Americans had higher frequencies of wild-type alleles for all genes, and lower frequency of CYP2D641, CYP2C92, and CYP2C1917 (p <0.05). Native Americans also showed less CYP2C19 gUMs than the rest of the population sample. In addition, differences within Native Americans (mostly North vs. South were also found. The interethnic differences described supports the need for population-specific personalized and precision medicine programs for Native Americans. To the best of our knowledge, this is the largest study carried out in Native Americans and other Ibero-American populations analyzing CYP2D6, CYP2C9, and CYP2C19 genetic polymorphisms. Population pharmacogenomics is a nascent field of global health and warrants further research and education.

Original languageEnglish (US)
Pages (from-to)575-588
Number of pages14
JournalOMICS A Journal of Integrative Biology
Volume22
Issue number9
DOIs
StatePublished - Sep 2018
Externally publishedYes

Keywords

  • Amerindians
  • CYP2C19
  • CYP2C9
  • CYP2D6
  • Latin Americans
  • Pharmacogenetics
  • drug metabolism
  • precision medicine

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

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