Pharmacogenetic Testing in Admixed Populations

Abstract

This article examines the frequency distribution of tier 1 pharmacogenetic variants of the Association for Molecular Pathology Pharmacogenomics Working Group Recommendations in two large (>1000 individuals) cohorts of the admixed Brazilian population, and in patients from the Brazilian Public Health System enrolled in pharmacogenetic trials. Three tier 1 variants, all in DPYD, were consistently absent, which may justify their noninclusion in genotyping panels for Brazilians; 13 variants had frequency ≤1.0%, and the remaining 21 variants ranged in frequency from 1.2% (NUDT15∗3) to 76.4% (CYP3A5∗3). The frequency of some CYP2C9, CYP2D6, CYP3A4, and VKORC1 variants differed significantly across the three major race/color categories of the Brazilian Census (White, Brown, and Black), as a consequence of different proportions of individual European and African ancestry. However, it is recommended that selection of variants for inclusion in pharmacogenetic testing panels and implementation of pharmacogenetic-informed dosing guidelines for Brazilians should not be determined by race/color categories. Native Americans (0.4% of the Brazilian population), virtually absent from the study cohorts, display wide interethnic diversity in frequency of some tier 1 variants (eg, NUDT15∗3 and TPMT∗3A) and/or differ markedly from non-Indigenous people in frequency of some variant alleles (eg, CYP2C19∗17). Collectively, the data support the notion that population diversity must be taken into account on the design and implementation of pharmacogenetic testing panels.