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PLoS One. 2014 Nov 24;9(11):e112640. doi: 10.1371/journal.pone.0112640. eCollection 2014.

Exploring the distribution of genetic markers of pharmacogenomics relevance in Brazilian and Mexican populations.

Author information

1
Computational Genomics Consortium, National Institute of Genomic Medicine, Mexico City, Mexico.
2
Nutrigenetics and Nutrigenomics Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
3
Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
4
Departamento de Radiologia e Oncologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
5
Computational Genomics Consortium, National Institute of Genomic Medicine, Mexico City, Mexico; Institute of Mathematical Sciences, Claremont Graduate University, Claremont, California, United States of America.
6
Genotyping and Expression Analysis Unit, National Institute of Genomic Medicine, Mexico City, Mexico.
7
DeBartolo Family Personalized Medicine Institute, University of South Florida Moffitt Cancer Center, Tampa, Florida, United States of America; Pharmacogenomics Department, Pharmacogenetics for Every Nation Initiative, Tampa, Florida, United States of America.
8
Cancer Genomics Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
9
Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.
10
Divisão de Farmacologia, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Studies of pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. However, the effect of the polymorphisms can differ in magnitude or be absent depending on the population being assessed. We used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array to characterize the distribution of polymorphisms of pharmacogenetics and pharmacogenomics (PGx) relevance in two samples from the most populous Latin American countries, Brazil and Mexico. The sample from Brazil included 268 individuals from the southeastern state of Rio de Janeiro, and was stratified into census categories. The sample from Mexico comprised 45 Native American Zapotecas and 224 self-identified Mestizo individuals from 5 states located in geographically distant regions in Mexico. We evaluated the admixture proportions in the Brazilian and Mexican samples using a panel of Ancestry Informative Markers extracted from the DMET array, which was validated with genome-wide data. A substantial variation in ancestral proportions across census categories in Brazil, and geographic regions in Mexico was identified. We evaluated the extent of genetic differentiation (measured as FST values) of the genetic markers of the DMET Plus array between the relevant parental populations. Although the average levels of genetic differentiation are low, there is a long tail of markers showing large frequency differences, including markers located in genes belonging to the Cytochrome P450, Solute Carrier (SLC) and UDP-glucuronyltransferase (UGT) families as well as other genes of PGx relevance such as ABCC8, ADH1A, CHST3, PON1, PPARD, PPARG, and VKORC1. We show how differences in admixture history may have an important impact in the distribution of allele and genotype frequencies at the population level.

PMID:
25419701
PMCID:
PMC4242606
DOI:
10.1371/journal.pone.0112640
[Indexed for MEDLINE]
Free PMC Article

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