title: Exploring the distribution of genetic markers of pharmacogenomics relevance in Brazilian and Mexican populations.
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.
authors.affiliation: Computational Genomics Consortium, National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: Vania
authors.initials: V
authors.lastname: Bonifaz-Peña
authors.affiliation: Nutrigenetics and Nutrigenomics Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: Alejandra V
authors.initials: AV
authors.lastname: Contreras
authors.affiliation: Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Claudio Jose
authors.initials: CJ
authors.lastname: Struchiner
authors.affiliation: Departamento de Radiologia e Oncologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Rosimeire A
authors.initials: RA
authors.lastname: Roela
authors.affiliation: Departamento de Radiologia e Oncologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Tatiane K
authors.initials: TK
authors.lastname: Furuya-Mazzotti
authors.affiliation: Departamento de Radiologia e Oncologia, Universidade de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Computational Genomics Consortium, National Institute of Genomic Medicine, Mexico City, Mexico; Institute of Mathematical Sciences, Claremont Graduate University, Claremont, California, United States of America.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rangel-Escareño
authors.affiliation: Genotyping and Expression Analysis Unit, National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: Laura
authors.initials: L
authors.lastname: Uribe-Figueroa
authors.affiliation: Computational Genomics Consortium, National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: María José
authors.initials: MJ
authors.lastname: Gómez-Vázquez
authors.affiliation: 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.
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.affiliation: Cancer Genomics Laboratory, National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.affiliation: Department of Anthropology, University of Toronto at Mississauga, Mississauga, Ontario, Canada.
authors.forename: Esteban J
authors.initials: EJ
authors.lastname: Parra
authors.affiliation: Computational Genomics Consortium, National Institute of Genomic Medicine, Mexico City, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Fernández-López
authors.affiliation: Divisão de Farmacologia, Instituto Nacional de Câncer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
mesh_terms: D001938:Brazil; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005787:Gene Frequency; D056426:Genetic Loci / Q000235:genetics*; D005828:Genetics, Population / Q000379:methods; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008800:Mexico; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D000099148:UGT1A1 Enzyme
chemical_list: D019389:Cytochrome P-450 CYP2D6; D014453:Glucuronosyltransferase; D064417:Vitamin K Epoxide Reductases; D000099148:UGT1A1 Enzyme; C578523:VKORC1 protein, human