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Distribution of a novel CYP2C haplotype in Native American populations.
Fernandes, Vanessa Câmara; Pretti, Marco Antônio M; Tsuneto, Luiza Tamie; Petzl-Erler, Maria Luiza; Suarez-Kurtz, Guilherme.
Afiliação
  • Fernandes VC; Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
  • Pretti MAM; Laboratório de Bioinformática e Biologia Computacional, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
  • Tsuneto LT; Departamento de Análises Clínicas, Universidade Estadual de Maringá, Maringá, Brazil.
  • Petzl-Erler ML; Programa de Pós-Graduação em Genética, Departamento de Genética, Universidade Federal do Paraná, Curitiba, Brazil.
  • Suarez-Kurtz G; Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Front Genet ; 14: 1114742, 2023.
Article em En | MEDLINE | ID: mdl-37025454
The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014-to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Genet Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Genet Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça