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Title: | Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A > G Variant Is Determinant of Increased Atorvastatin Response |
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. |
Citation: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.12, n.9, p.5815-5827, 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 (R) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan (R) 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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - HU |
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