Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response |
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Authors: | 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 |
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Affiliation: | Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-900, Brazil; E-Mails: paulamsp@gmail.com (P.M.S.P.); viviansilbiger@hotmail.com (V.N.S.); fdallavecchia@yahoo.com.br (F.D.V.G.); malicewi@usp.br (M.A.V.W.); sisorkin@usp.br (S.S.A.); adluchessi@uol.com.br (A.D.L.); mhhirata@usp.br (M.H.H.); rosariohirata@usp.br (R.D.C.H.). |
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Abstract: | AimsThe relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated.Material and MethodsOne-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.ResultsSubjects 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).ConclusionSLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy. |
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Keywords: | OATP atorvastatin single nucleotide polymorphisms pharmacogenetics |
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