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Open Access 01-12-2016 | Research article

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

Authors: Rafael B. R. León-Cachón, Jorge A. Ascacio-Martínez, María E. Gamino-Peña, Ricardo M. Cerda-Flores, Irene Meester, Hugo L. Gallardo-Blanco, Magdalena Gómez-Silva, Everardo Piñeyro-Garza, Hugo A. Barrera-Saldaña

Published in: BMC Cancer | Issue 1/2016

Abstract

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.

Trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12614000851662, date registered: August 8, 2014.

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Title: A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers
Authors: Rafael B. R. León-Cachón
Jorge A. Ascacio-Martínez
María E. Gamino-Peña
Ricardo M. Cerda-Flores
Irene Meester
Hugo L. Gallardo-Blanco
Magdalena Gómez-Silva
Everardo Piñeyro-Garza
Hugo A. Barrera-Saldaña
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2062-2

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