TY - JOUR
T1 - Interethnic variability in CYP2D6, CYP2C9, and CYP2C19 genes and predicted drug metabolism phenotypes among 6060 ibero-and native Americans
T2 - RIBEF-CEIBA consortium report on population pharmacogenomics
AU - Naranjo, María Eugenia G.
AU - Rodrigues-Soares, Fernanda
AU - Peñas-Lledó, Eva M.
AU - Tarazona-Santos, Eduardo
AU - Fariñas, Humberto
AU - Rodeiro, Idania
AU - Terán, Enrique
AU - Grazina, Manuela
AU - Moya, Graciela E.
AU - López-López, Marisol
AU - Sarmiento, Alba P.
AU - Calzadilla, Luis R.
AU - Ramírez-Roa, Ronald
AU - Ortiz-López, Rocío
AU - Estévez-Carrizo, Francisco E.
AU - Sosa-Macías, Martha
AU - Barrantes, Ramiro
AU - Lerena, Adrián L.
AU - Fcrreiro, Verónica
AU - Scliar, Marilia O.
AU - Gouveia, Mateus H.
AU - Borbon, Angelica
AU - Jiménez-Arce, Gerardo
AU - Céspedes-Garro, Carolina
AU - Álvárez, Mayra
AU - Delgado, René
AU - Remirez, Diadelis
AU - Pérez, Bárbaro
AU - Hernández, Francisco
AU - Terán, Santiago
AU - Rojas-Martinez, Augusto
AU - Garza-Ocañas, Lourdes
AU - Pérez-Páramo, Yadira X.
AU - Ortega-Vázquez, Alberto
AU - Monroy-Jaramillo, Nancy
AU - Jung-Cook, Helgi
AU - Fricke-Galindo, Ingrid
AU - Galaviz-Hernández, Carlos
AU - Lares-Aseff, Ismael
AU - Lazalde-Ramos, Blanca P.
AU - Tinoco, Catalina Altamirano
AU - Zamudio, Roxana
AU - Gilman, Robert H.
AU - Cobaleda, Jesús
AU - de Andrés, Fernando
AU - Dorado, Pedro
N1 - Publisher Copyright:
© Mary Ann Liebert, Inc.
PY - 2018/9
Y1 - 2018/9
N2 - 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 CYP2D6∗41, CYP2C9∗2, and CYP2C19∗17 (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.
AB - 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 CYP2D6∗41, CYP2C9∗2, and CYP2C19∗17 (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.
KW - Amerindians
KW - CYP2C19
KW - CYP2C9
KW - CYP2D6
KW - Latin Americans
KW - Pharmacogenetics
KW - drug metabolism
KW - precision medicine
UR - http://www.scopus.com/inward/record.url?scp=85053861167&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053861167&partnerID=8YFLogxK
U2 - 10.1089/omi.2018.0114
DO - 10.1089/omi.2018.0114
M3 - Article
C2 - 30183544
AN - SCOPUS:85053861167
SN - 1536-2310
VL - 22
SP - 575
EP - 588
JO - OMICS A Journal of Integrative Biology
JF - OMICS A Journal of Integrative Biology
IS - 9
ER -