Next Article in Journal
Efficient 1H-NMR Quantitation and Investigation of N-Acetyl-D-glucosamine (GlcNAc) and N,N'-Diacetylchitobiose (GlcNAc)2 from Chitin
Next Article in Special Issue
Tunicamycin Depresses P-Glycoprotein Glycosylation Without an Effect on Its Membrane Localization and Drug Efflux Activity in L1210 Cells
Previous Article in Journal
Role of α-Helical Structure in Organic Solvent-Activated Homodimer of Elastase Strain K
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2011, 12(9), 5815-5827; doi:10.3390/ijms12095815

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

1
Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
2
Life Technologies, Sao Paulo 04311-000, Brazil
3
University Hospital, University of Sao Paulo, Sao Paulo 05508-000, Brazil
4
Department of Biology, University of Aveiro, Aveiro 3810-193, Portugal
5
Forensic Genetics Unit, Institute of Legal Medicine, University of Santiago de Compostela, Galicia 15705, Spain
6
Dante Pazzanese Institute, Sao Paulo 04012-909, Brazil
*
Author to whom correspondence should be addressed.
Received: 29 July 2011 / Revised: 29 August 2011 / Accepted: 30 August 2011 / Published: 9 September 2011
(This article belongs to the Special Issue Membrane Transport)
View Full-Text   |   Download PDF [333 KB, uploaded 19 June 2014]   |  

Abstract

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy. View Full-Text
Keywords: OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material

Share & Cite This Article

MDPI and ACS Style

Rodrigues, A.C.; Perin, P.M.S.; Purim, S.G.; Silbiger, V.N.; Genvigir, F.D.V.; Willrich, M.A.V.; Arazi, S.S.; Luchessi, A.D.; Hirata, M.H.; Bernik, M.M.S.; Dorea, E.L.; Santos, C.; Faludi, A.A.; Bertolami, M.C.; Salas, A.; Freire, A.; Lareu, M.V.; Phillips, C.; Porras-Hurtado, L.; Fondevila, M.; Carracedo, A.; Hirata, R.D.C. Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response. Int. J. Mol. Sci. 2011, 12, 5815-5827.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top