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. 2020 Jan;107(1):257-268.
doi: 10.1002/cpt.1598. Epub 2019 Oct 7.

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

Fernanda Rodrigues-Soares  1   2   3 , Eva M Peñas-Lledó  1   4 , Eduardo Tarazona-Santos  1   2   5   6 , Martha Sosa-Macías  1   7 , Enrique Terán  1   8 , Marisol López-López  1   9 , Idania Rodeiro  1   10 , Graciela E Moya  1   11 , Luis R Calzadilla  1   12 , Ronald Ramírez-Roa  1   13 , Manuela Grazina  1   14 , Francisco E Estévez-Carrizo  1   15 , Ramiro Barrantes  1   16 , Adrián LLerena  1   4 ; RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics
Collaborators, Affiliations

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

Fernanda Rodrigues-Soares et al. Clin Pharmacol Ther. 2020 Jan.

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.

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