A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers

León Cachón, Rafael B. R. y Ascacio Martínez, Jorge Ángel Isidro y Gamino Peña, María E. y Cerda Flores, Ricardo Martín y Meester, Irene y Gallardo Blanco, Hugo Leonid y Gómez Silva, Magdalena y Piñeyro Garza, Everardo y Barrera Saldaña, Hugo Alberto (2016) A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers. BMC cancer, 16 (1). pp. 1-13. ISSN 1471-2407

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URL o página oficial: http://doi.org/10.1186/s12885-016-2062-2

Resumen

Background: The genetic variation underlying atorvastatin (ATV) pharmacokinetics was evaluated in a Mexican population. Aims of this study were: 1) to reveal the frequency of 87 polymorphisms in 36 genes related to drug metabolism in healthy Mexican volunteers, 2) to evaluate the impact of these polymorphisms on ATV pharmacokinetics, 3) to classify the ATV metabolic phenotypes of healthy volunteers, and 4) to investigate a possible association between genotypes and metabolizer phenotypes. Methods: A pharmacokinetic study of ATV (single 80-mg dose) was conducted in 60 healthy male volunteers. ATV plasma concentrations were measured by high-performance liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated by the non-compartmental method. The polymorphisms were determined with the PHARMAchip® microarray and the TaqMan® probes genotyping assay. Results: Three metabolic phenotypes were found in our population: slow, normal, and rapid. Six gene polymorphisms were found to have a significant effect on ATV pharmacokinetics: MTHFR (rs1801133), DRD3 (rs6280), GSTM3 (rs1799735), TNFα (rs1800629), MDR1 (rs1045642), and SLCO1B1 (rs4149056). The combination of MTHFR, DRD3 and MDR1 polymorphisms associated with a slow ATV metabolizer phenotype. Conclusion: Further studies using a genetic preselection method and a larger population are needed to confirm these polymorphisms as predictive biomarkers for ATV slow metabolizers.

Tipo de elemento:

Article

Palabras claves no controlados:

Atorvastatin, Genotype phenotype association, Predictive genetic testing

Divisiones:

Medicina

Usuario depositante:

Editor Repositorio

Creadores:

Creador	Email	ORCID
León Cachón, Rafael B. R.	NO ESPECIFICADO	NO ESPECIFICADO
Ascacio Martínez, Jorge Ángel Isidro	NO ESPECIFICADO	NO ESPECIFICADO
Gamino Peña, María E.	NO ESPECIFICADO	NO ESPECIFICADO
Cerda Flores, Ricardo Martín	NO ESPECIFICADO	NO ESPECIFICADO
Meester, Irene	NO ESPECIFICADO	NO ESPECIFICADO
Gallardo Blanco, Hugo Leonid	hugo.gallardobl@uanl.edu.mx	NO ESPECIFICADO
Gómez Silva, Magdalena	NO ESPECIFICADO	NO ESPECIFICADO
Piñeyro Garza, Everardo	NO ESPECIFICADO	NO ESPECIFICADO
Barrera Saldaña, Hugo Alberto	habarrera@gmail.com	orcid.org/0000-0003-1587-4571