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Genetic structure of pharmacogenetic biomarkers in Brazil inferred from a systematic review and population-based cohorts: a RIBEF/EPIGEN-Brazil initiative

Abstract

We present allele frequencies involving 39 pharmacogenetic biomarkers studied in Brazil, and their distribution on self-reported race/color categories that: (1) involve a mix of perceptions about ancestry, morphological traits, and cultural/identity issues, being social constructs pervasively used in Brazilian society and medical studies; (2) are associated with disparities in access to health services, as well as in their representation in genetic studies, and (3), as we report here, explain a larger portion of the variance of pharmaco-allele frequencies than geography. We integrated a systematic review of studies on healthy volunteers (years 1968–2017) and the analysis of allele frequencies on three population-based cohorts from northeast, southeast, and south, the most populated regions of Brazil. Cross-validation of results from these both approaches suggest that, despite methodological heterogeneity of the 120 studies conducted on 51,747 healthy volunteers, allele frequencies estimates from systematic review are reliable. We report differences in allele frequencies between color categories that persist despite the homogenizing effect of >500 years of admixture. Among clinically relevant variants: CYP2C9*2 (null), CYP3A5*3 (defective), SLCO1B1-rs4149056(C), and VKORC1-rs9923231(A) are more frequent in Whites than in Blacks. Brazilian Native Americans show lower frequencies of CYP2C9*2, CYP2C19*17 (increased activity), and higher of SLCO1B1-rs4149056(C) than other Brazilian populations. We present the most current and informative database of pharmaco-allele frequencies in Brazilian healthy volunteers.

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Acknowledgements

We thank RIBEF/MESTIFAR members for interactions, to Daniela Junqueira, Maria Clara da Silva, Maria B Lovato, and Renan P Souza for discussions.

Funding

CAPES Foundation from the Brazilian Ministry of Education, Brazilian National Research Council (CNPq), Minas Gerais State Agency for Research (FAPEMIG). The EPIGEN-Brazil Initiative was funded by the Brazilian Ministry of Health (Secretaria de Ciência, Tecnologia e Insumos Estratégicos [SCTIE]), through Financiadora de Estudos e Projetos (FINEP).

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Rodrigues-Soares, F., Kehdy, F.S.G., Sampaio-Coelho, J. et al. Genetic structure of pharmacogenetic biomarkers in Brazil inferred from a systematic review and population-based cohorts: a RIBEF/EPIGEN-Brazil initiative. Pharmacogenomics J 18, 749–759 (2018). https://doi.org/10.1038/s41397-018-0015-7

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