A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers
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 pol...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2016
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| Online Access: | http://eprints.uanl.mx/14840/1/55.pdf |
| _version_ | 1824414159158116352 |
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| author | León Cachón, Rafael B. R. Ascacio Martínez, Jorge Ángel Isidro Gamino Peña, María E. Cerda Flores, Ricardo Martín Meester, Irene Gallardo Blanco, Hugo Leonid Gómez Silva, Magdalena Piñeyro Garza, Everardo Barrera Saldaña, Hugo Alberto |
| author_facet | León Cachón, Rafael B. R. Ascacio Martínez, Jorge Ángel Isidro Gamino Peña, María E. Cerda Flores, Ricardo Martín Meester, Irene Gallardo Blanco, Hugo Leonid Gómez Silva, Magdalena Piñeyro Garza, Everardo Barrera Saldaña, Hugo Alberto |
| author_sort | León Cachón, Rafael B. R. |
| collection | Repositorio Institucional |
| description | 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. |
| format | Article |
| id | eprints-14840 |
| institution | UANL |
| language | English |
| publishDate | 2016 |
| publisher | BMC |
| record_format | eprints |
| spelling | eprints-148402024-12-09T17:46:53Z http://eprints.uanl.mx/14840/ A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers León Cachón, Rafael B. R. Ascacio Martínez, Jorge Ángel Isidro Gamino Peña, María E. Cerda Flores, Ricardo Martín Meester, Irene Gallardo Blanco, Hugo Leonid Gómez Silva, Magdalena Piñeyro Garza, Everardo Barrera Saldaña, Hugo Alberto 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. BMC 2016 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/14840/1/55.pdf http://eprints.uanl.mx/14840/1.haspreviewThumbnailVersion/55.pdf 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 http://doi.org/10.1186/s12885-016-2062-2 doi:10.1186/s12885-016-2062-2 |
| spellingShingle | León Cachón, Rafael B. R. Ascacio Martínez, Jorge Ángel Isidro Gamino Peña, María E. Cerda Flores, Ricardo Martín Meester, Irene Gallardo Blanco, Hugo Leonid Gómez Silva, Magdalena Piñeyro Garza, Everardo Barrera Saldaña, Hugo Alberto A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| title_full | A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| title_fullStr | A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| title_full_unstemmed | A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| title_short | A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| title_sort | pharmacogenetic pilot study reveals mthfr drd3 and mdr1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers |
| url | http://eprints.uanl.mx/14840/1/55.pdf |
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