RT Journal Article
T1 Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response
A1 Rodrigues, Alice C.
A1 Santos, Carla
A1 Salas Ellacuriaga, Antonio
A1 Freire Aradas, Ana María
A1 Lareu Huidobro, María Victoria
A1 Phillips, Christopher Paul
A1 Porras Hurtado, Gloria Liliana
A1 Fondevila Álvarez, Manuel
A1 Carracedo Álvarez, Ángel
A1 Hirata, Rosario D. C.
K1 OATP
K1 Atorvastatin
K1 Single nucleotide polymorphisms
K1 Pharmacogenetics
AB 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.
PB MDPI
YR 2011
FD 2011
LK http://hdl.handle.net/10347/21660
UL http://hdl.handle.net/10347/21660
LA eng
NO 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
NO This work was supported by grants from FAPESP (2008/06667-9). A.C. Rodrigues, F.D.V.Genvigir and M.A.V. Willrich are recipients of fellowships from FAPESP, Sao Paulo, Brazil. M.H.Hirata and R.D.C. Hirata are recipients of fellowships from CNPq, Brasilia, Brazil.This work was partially supported by Life Technologies, Sao Paulo, SP, Brazil
DS Minerva
RD 3 may 2026