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. Scliar; Mateus 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

doi:10.1089/omi.2018.0114

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. Scliar

Mateus 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

^*Corresponding author for this work

RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics
University of Extremadura
University of Castilla-La Mancha
Clinical Research Center University Hospital
Universidad Pablo de Olavide-CSIC-Junta de Andalucý́a
Universidade Federal de Minas Gerais
Faculdade Uninassau
Asociación Benéfica Prisma
Universidad Peruana Cayetano Heredia
PRISMA Asociación Benéfica
Instituto de Ciencias del Mar
Centro de Bioproductos Marinos
Universidad de Guayaquil
University of Coimbra, Center for Neuroscience and Cell Biology
Pontificia Universidad Católica Argentina Santa María de los Buenos Aires - UCA
Fundación GENOS
Universidad Autónoma Metropolitana
Instituto Nacional de Neurologia y Neurocirugia
Universidad Nacional Autónoma de México
Universidad Javeriana
Centro Comunitario de Salud Mental de la Habana Vieja
Facultad de Ciencias Médicas Calixto García
Centro para las Investigaciones y Desarrollo de los Medicamentos
Centro para el Control Estatal Calidad de los Medicamentos
Centro Communitario de Salud Mental La Habana Vieja
Universidad Nacional Autónoma de Nicaragua
Instituto Tecnologico de Estudios Superiores de Monterrey
Universidad Autonoma de Nuevo Leon
Universidad de Montevideo
IPN
Universidad Autonoma de Zacatecas
University of Costa Rica
Faculdade Maurício de Uninassau
Universidad San Francisco de Quito

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

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 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.

Original language	English
Pages (from-to)	575-588
Number of pages	14
Journal	OMICS A Journal of Integrative Biology
Volume	22
Issue number	9
DOIs	https://doi.org/10.1089/omi.2018.0114
State	Published - Sep 2018

Keywords

Amerindians
CYP2C19
CYP2C9
CYP2D6
Latin Americans
Pharmacogenetics
drug metabolism
precision medicine

Access to Document

10.1089/omi.2018.0114

Cite this

Naranjo, M. E. G., Rodrigues-Soares, F., Peñas-Lledó, E. M., Tarazona-Santos, E., Fariñas, H., Rodeiro, I., Terán, E., Grazina, M., Moya, G. E., López-López, M., Sarmiento, A. P., Calzadilla, L. R., Ramírez-Roa, R., Ortiz-López, R., Estévez-Carrizo, F. E., Sosa-Macías, M., Barrantes, R., Lerena, A. L., Fcrreiro, V., ... Dorado, P. (2018). 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. OMICS A Journal of Integrative Biology, 22(9), 575-588. https://doi.org/10.1089/omi.2018.0114

Naranjo, María Eugenia G. ; Rodrigues-Soares, Fernanda ; Peñas-Lledó, Eva M. et al. / 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. In: OMICS A Journal of Integrative Biology. 2018 ; Vol. 22, No. 9. pp. 575-588.

@article{5f41e077448f4630814bb2bfc4d794ad,

title = "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",

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 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.",

keywords = "Amerindians, CYP2C19, CYP2C9, CYP2D6, Latin Americans, Pharmacogenetics, drug metabolism, precision medicine",

author = "Naranjo, \{Mar{\'i}a Eugenia G.\} and Fernanda Rodrigues-Soares and Pe{\~n}as-Lled{\'o}, \{Eva M.\} and Eduardo Tarazona-Santos and Humberto Fari{\~n}as and Idania Rodeiro and Enrique Ter{\'a}n and Manuela Grazina and Moya, \{Graciela E.\} and Marisol L{\'o}pez-L{\'o}pez and Sarmiento, \{Alba P.\} and Calzadilla, \{Luis R.\} and Ronald Ram{\'i}rez-Roa and Roc{\'i}o Ortiz-L{\'o}pez and Est{\'e}vez-Carrizo, \{Francisco E.\} and Martha Sosa-Mac{\'i}as and Ramiro Barrantes and Lerena, \{Adri{\'a}n L.\} and Ver{\'o}nica Fcrreiro and Scliar, \{Marilia O.\} and Gouveia, \{Mateus H.\} and Angelica Borbon and Gerardo Jim{\'e}nez-Arce and Carolina C{\'e}spedes-Garro and Mayra {\'A}lv{\'a}rez and Ren{\'e} Delgado and Diadelis Remirez and B{\'a}rbaro P{\'e}rez and Francisco Hern{\'a}ndez and Santiago Ter{\'a}n and Augusto Rojas-Martinez and Lourdes Garza-Oca{\~n}as and P{\'e}rez-P{\'a}ramo, \{Yadira X.\} and Alberto Ortega-V{\'a}zquez and Nancy Monroy-Jaramillo and Helgi Jung-Cook and Ingrid Fricke-Galindo and Carlos Galaviz-Hern{\'a}ndez and Ismael Lares-Aseff and Lazalde-Ramos, \{Blanca P.\} and Tinoco, \{Catalina Altamirano\} and Roxana Zamudio and Gilman, \{Robert H.\} and Jes{\'u}s Cobaleda and \{de Andr{\'e}s\}, Fernando and Pedro Dorado",

note = "Publisher Copyright: {\textcopyright} Mary Ann Liebert, Inc.",

year = "2018",

month = sep,

doi = "10.1089/omi.2018.0114",

language = "Ingl{\'e}s",

volume = "22",

pages = "575--588",

journal = "OMICS A Journal of Integrative Biology",

issn = "1536-2310",

publisher = "SAGE Publications Ltd",

number = "9",

}

Naranjo, MEG, Rodrigues-Soares, F, Peñas-Lledó, EM, Tarazona-Santos, E, Fariñas, H, Rodeiro, I, Terán, E, Grazina, M, Moya, GE, López-López, M, Sarmiento, AP, Calzadilla, LR, Ramírez-Roa, R, Ortiz-López, R, Estévez-Carrizo, FE, Sosa-Macías, M, Barrantes, R, Lerena, AL, Fcrreiro, V, Scliar, MO, Gouveia, MH, Borbon, A, Jiménez-Arce, G, Céspedes-Garro, C, Álvárez, M, Delgado, R, Remirez, D, Pérez, B, Hernández, F, Terán, S, Rojas-Martinez, A, Garza-Ocañas, L, Pérez-Páramo, YX, Ortega-Vázquez, A, Monroy-Jaramillo, N, Jung-Cook, H, Fricke-Galindo, I, Galaviz-Hernández, C, Lares-Aseff, I, Lazalde-Ramos, BP, Tinoco, CA, Zamudio, R, Gilman, RH, Cobaleda, J, de Andrés, F & Dorado, P 2018, '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', OMICS A Journal of Integrative Biology, vol. 22, no. 9, pp. 575-588. https://doi.org/10.1089/omi.2018.0114

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. / Naranjo, María Eugenia G.; Rodrigues-Soares, Fernanda; Peñas-Lledó, Eva M. et al.
In: OMICS A Journal of Integrative Biology, Vol. 22, No. 9, 09.2018, p. 575-588.

Research output: Contribution to journal › Article › peer-review

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

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 - https://www.scopus.com/pages/publications/85053861167

U2 - 10.1089/omi.2018.0114

DO - 10.1089/omi.2018.0114

M3 - Artículo

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 -

Naranjo MEG, Rodrigues-Soares F, Peñas-Lledó EM, Tarazona-Santos E, Fariñas H, Rodeiro I et al. 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. OMICS A Journal of Integrative Biology. 2018 Sep;22(9):575-588. doi: 10.1089/omi.2018.0114

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

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