期刊
MOLECULAR BIOLOGY REPORTS
卷 41, 期 3, 页码 1453-1460出版社
SPRINGER
DOI: 10.1007/s11033-013-2990-8
关键词
Polymorphisms; Variability; Pharmacogenetics; Cytochrome P450; Ethnicity; Brazil
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES
- Brazil)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)
- Programa de Apoio a Nucleos de Excelencia (PRONEX, Brazil)
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS, Brazil)
- Fundacao Carlos Chagas Filho de Amparo a pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil)
- FIS (ISCIII, Spain) [PI071032, PI061712]
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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