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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.

Distribution of CYP2D6 Alleles and Phenotypes in the Brazilian Population