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Characterization of CYP1A2, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in South Brazilians

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Abstract

Potential causes of variability in drug response include intrinsic factors such as ethnicity and genetic differences in the expression of enzymes that metabolize drugs, such as those from Cytochrome P450 (CYPs) superfamily. Pharmacogenetic studies search for genetic differences between populations since relevant alleles occur with varying frequencies among different ethnic populations. The Brazilian population is one of the most heterogeneous in the world, resulting from multiethnic admixture of Amerindians, Europeans, and Africans across centuries. Since the knowledge of CYP allele frequency distributions is relevant to pharmacogenetic strategies and these data are scarce in the Brazilian population, this study aimed to describe genotype and allele distributions of 15 single nucleotide polymorphisms (SNPs) at CYP 1A2, 2C19, 3A4, and 3A5 genes in African and European descents from South Brazil. A sample of 179 healthy individuals of European and African ancestry was genotyped by the MassARRAY SNP genotyping system. CYP3A5*3, CYP1A2*1F, CYP3A4*1B, and CYP2C19*2 were the most frequent alleles found in our sample. Significant differences in genotype and allelic distribution between African and European descents were observed for CYP3A4 and CYP3A5 genes. CYP3A4*1B was observed in higher frequency in African descents (0.379) than in European descents (0.098), and European descents showed higher frequency of CYP3A5*3 (0.810) than African descents (0.523). Our results indicate that only a few polymorphisms would have impact in pharmacogenetic testing in South Brazilians. Further studies with larger sample sizes are required also among other Brazilian regions.

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Acknowledgments

The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Brazil) for the fellowship to F.B.K. to perform part of this study in Spain. Financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Programa de Apoio a Núcleos de Excelência (PRONEX, Brazil), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Brazil), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil), Fundação Carlos Chagas Filho de Amparo à pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil), and FIS grants PI071032 and PI061712 (ISCIII, Spain).

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  1. Departamento de Biologia Geral, Instituto de Biologia, Universidade Federal Fluminense (UFF), Niterói, RJ, CEP 24061-970, Brazil

    Fabiana B. Kohlrausch

  2. Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Fabiana B. Kohlrausch & Mara H. Hutz

  3. Fundación Pública Galega de Medicina Xenómica, Grupo de Medicina Xenómica, CIBERER, Santiago de Compostela, Spain

    Ángel Carracedo

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  1. Fabiana B. Kohlrausch
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Correspondence to Fabiana B. Kohlrausch.

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Kohlrausch, F.B., Carracedo, Á. & Hutz, M.H. Characterization of CYP1A2, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in South Brazilians. Mol Biol Rep 41, 1453–1460 (2014). https://doi.org/10.1007/s11033-013-2990-8

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