title: Distribution of CYP2D6 alleles and phenotypes in the Brazilian population.
abstract: The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The CYP2D6 gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of CYP2D6 alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and CYP2D6 duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen CYP2D6 alleles were identified in the Brazilian population. The CYP2D6*1 and CYP2D6*2 alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of CYPD6 alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil) to 10.2% (Northern Brazil). The analysis of molecular variance showed that CYP2D6 is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%). Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique CYP2D6 testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Deise C
authors.initials: DC
authors.lastname: Friedrich
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Júlia P
authors.initials: JP
authors.lastname: Genro
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Vinicius A
authors.initials: VA
authors.lastname: Sortica
authors.affiliation: Programa de Farmacologia, Instituto Nacional de Cancer, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Maria Elizabete
authors.initials: ME
authors.lastname: de Moraes
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sergio D J
authors.initials: SD
authors.lastname: Pena
authors.affiliation: Laboratório de Genética Humana e Medica, Universidade Federal do Pará, Belém, Pará, Brazil.
authors.forename: Andrea K Ribeiro
authors.initials: AK
authors.lastname: dos Santos
authors.affiliation: Instituto Nacional de Ciência e Tecnologia de Medicina Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Romano-Silva
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D000483:Alleles; D044383:Black People; D001938:Brazil; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D005787:Gene Frequency; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D019389:Cytochrome P-450 CYP2D6