Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 107, Issue 1, Pages 257-268Publisher
WILEY
DOI: 10.1002/cpt.1598
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Funding
- Junta Extremadura-AEXCID (PATLI) [18IA003]
- Brazilian National Research Council (CNPq)
- Coordination for the Improvement of Higher Education Personnel -Brazilian Ministry of Education (CAPES)
- Pro-Reitoria de Pesquisa-Universidade Federal de Minas Gerais
- CAPES-PDSE fellowship
- Universidad San Francisco de Quito
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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 CYP2C19gUMs (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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