Molecular diversity at the CYP2D6 locus in healthy and schizophrenic southern Brazilians

The delineation of allele distribution and frequency is required to effectively translate pharmacogenetics to the clinic and given the paucity of CYP2D6 data in the Brazilian population, the purpose of this research was to characterize CYP2D6 alleles and genotype frequencies in Brazilians of European and African ancestries. Moreover, since it is suggested in the literature that CYP2D6 poor metabolism might be involved with susceptibility to schizophrenia, we included data from Brazilian schizophrenic patients to verify if CYP2D6 poor metabolism phenotypes are associated with susceptibility to schizophrenia.

We investigated 24 CYP2D6 polymorphisms, gene deletions and gene multiplications in 179 healthy individuals from Brazil, 92 of European descent and 87 African Brazilians. CYP2D6 gene polymorphisms were genotyped by a MassARRAY SNP genotyping system.

A total of 19 different alleles and five allele duplications were identified in African and European Brazilians. No significant differences in CYP2D6 allele function or poor metabolizer predicted phenotype frequencies were observed between healthy controls and schizophrenic patients, but the predicted metabolic phenotype distribution showed a significant higher frequency of intermediate metabolizers in African Brazilians than in European Brazilians (p = 0.001).

CYP2D6 poor metabolizer genotype seems not to be a determining factor of schizophrenia susceptibility in Brazilians. The characterization of CYP2D6 variability will be very useful for future pharmacogenetic studies in the Brazilian population.