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Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response
Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil
Life Technologies, Sao Paulo 04311-000, Brazil
University Hospital, University of Sao Paulo, Sao Paulo 05508-000, Brazil
Department of Biology, University of Aveiro, Aveiro 3810-193, Portugal
Forensic Genetics Unit, Institute of Legal Medicine, University of Santiago de Compostela, Galicia 15705, Spain
Dante Pazzanese Institute, Sao Paulo 04012-909, Brazil
* Author to whom correspondence should be addressed.
Received: 29 July 2011; in revised form: 29 August 2011 / Accepted: 30 August 2011 / Published: 9 September 2011
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
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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.
Rodrigues AC, Perin PMS, Purim SG, Silbiger VN, Genvigir FDV, Willrich MAV, Arazi SS, Luchessi AD, Hirata MH, Bernik MMS, Dorea EL, Santos C, Faludi AA, Bertolami MC, Salas A, Freire A, Lareu MV, Phillips C, Porras-Hurtado L, Fondevila M, Carracedo A, Hirata RDC. Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response. International Journal of Molecular Sciences. 2011; 12(9):5815-5827.
Rodrigues, Alice C.; Perin, Paula M. S.; Purim, Sheila G.; Silbiger, Vivian N.; Genvigir, Fabiana D. V.; Willrich, Maria Alice V.; Arazi, Simone S.; Luchessi, Andre D.; Hirata, Mario H.; Bernik, Marcia M. S.; Dorea, Egidio L.; Santos, Carla; Faludi, Andre A.; Bertolami, Marcelo C.; Salas, Antonio; Freire, Ana; Lareu, Maria V.; Phillips, Christopher; Porras-Hurtado, Liliana; Fondevila, Manuel; Carracedo, Angel; Hirata, Rosario D. C. 2011. "Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response." Int. J. Mol. Sci. 12, no. 9: 5815-5827.