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Genetic Diversity of Drug-Related Genes in Native Americans of the Brazilian Amazon

Authors Fernandes MR, Rodrigues JCG, Maroñas O, Latorre-Pellicer A, Cruz R, Guerreiro JF, Burbano RMR, Assumpção PP, Ribeiro-dos-Santos A, Santos SEB, Carracedo A, Santos NPC

Received 30 July 2020

Accepted for publication 23 October 2020

Published 22 January 2021 Volume 2021:14 Pages 117—133

DOI https://doi.org/10.2147/PGPM.S274741

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Martin Bluth


Marianne Rodrigues Fernandes,1,2 Juliana Carla Gomes Rodrigues,1 Olalla Maroñas,3 Ana Latorre-Pellicer,3,4 Raquel Cruz,5 João Farias Guerreiro,6 Rommel Mario Rodriguez Burbano,1,2 Paulo Pimentel de Assumpção,1 Andrea Ribeiro-dos-Santos,1,6 Sidney Emanuel Batista dos Santos,1,6 Angel Carracedo,3,5,7 Ney Pereira Carneiro dos Santos1

1Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Pará, Brazil; 2Departamento de ensino e pesquisa, Hospital Ophir Loyola, Belém, Pará, Brazil; 3Grupo de Medicina Xenómica, Centro Nacional de Genotipado (CEGEN-PRB3), Universidade de Santiago de Compostela, Santiago de Compostela, España; 4Unidad de Genética Clínica y Genómica Funcional, Departamento de Farmacología-Fisiología, Escuela de Medicina, Universidad de Zaragoza, IIS-Aragón, E-50009 Zaragoza, España; 5Centro de Investigación Biomédica en Enfermedades Raras (CIBERER), Grupo de Medicina Genómica, CIMUS, Universidad de Santiago de Compostela, Santiago de Compostela, España; 6Laboratório de Genética Humana e Médica, Universidade Federal do Pará, Belém, Pará, Brazil; 7Fundación Pública de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Universidade de Santiago de Compostela, Santiago de Compostela, España

Correspondence: Ney Pereira Carneiro dos Santos
Hospital Universitário João de Barros Barreto, Núcleo de Pesquisa em Oncologia, 2º Floor of the Unidade de Alta Complexidade em Oncologia. Av. Mundurucus, 4487, Guamá, Belém 66073-005, PA, Brazil
Tel +55 (91) 99113-9221
Email npcsantos.ufpa@gmail.com

Introduction: The genetic admixture of the Brazilian population has considerable relevance to the implementation of the principles of pharmacogenomics (PGx), as it may compromise the extrapolation of data obtained in more homogeneous world populations.
Purpose: This study aims to investigate a panel of 117 polymorphisms in 35 pharmacogenes, which contains label recommendations or clinical evidence by international drug regulatory agencies, in Amazonian Native American populations, and compare the results obtained with continental population data from the 1000 Genomes Project Consortium.
Patients and Methods: The study population is composed of 109 Native American individuals from three Brazilian Amazon groups. The genotyping of the PGx polymorphisms was performed by allelic discrimination using TaqMan® OpenArray Genotyping with a panel of 120 customized assays on the QuantStudio™ 12K Flex Real-Time PCR System.
Results: Statistical differences within the Native American populations were observed regarding both genotypes and phenotypes of some genes of the CYP family. The discriminant analysis of principal components (DAPCs) between the NAM group and the continental populations of the 1000 Genomes Project resulted in the clustering of the three Native American populations. Additionally, in general, the NAM group was determined to be closely situated between East Asia, America, and South Asia groups, which enabled us to infer a genetic similarity between these populations. The DAPC analysis further demonstrated that eight polymorphisms and six polymorphisms were more relevant in differentiating the NAM from the continental populations and the NAM populations among themselves, respectively.
Conclusion: Some investigated polymorphisms show differences among world populations, particularly with populations of European origin, for whom precision medicine protocols are primarily designed. The accumulated knowledge regarding these variations may assist in the design of specific protocols for Native American populations and populations admixed with them.

Keywords: Native Americans, pharmacogenomics, polymorphisms, population, genetic admixture, Brazil

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