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

RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalClinical pharmacology and therapeutics
DOIs
StateAccepted/In press - Jan 1 2019

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics (Accepted/In press). Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans. Clinical pharmacology and therapeutics. https://doi.org/10.1002/cpt.1598