Molecular Diversity at the CYP2D6 Locus in Healthy and Schizophrenic Southern Brazilians

Abstract

Aims: 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. Materials & methods: 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. Results: 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). Conclusions: 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.

KEYWORDS::

• Brazilians
• CYP2D6
• pharmacogenetics
• poor metabolizers
• schizophrenia
• variability

Financial & competing interests disclosure

Financial support was provided by Institutos do Milênio, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil) and FIS grants PI071032 and PI061712 (ISCIII, Spain). The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the fellowship to Fabiana B Kohlrausch to perform part of this study in Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Financial support was provided by Institutos do Milênio, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil) and Fidelity Information Services (FIS) grants PI071032 and PI061712 (ISCIII, Spain). The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the fellowship to Fabiana B Kohlrausch to perform part of this study in Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.