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

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

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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)
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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.
Keywords: OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics OATP; atorvastatin; single nucleotide polymorphisms; pharmacogenetics
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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