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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Rodrigues, Alice C. [1] ; Perin, Paula M. S. [1] ; Purim, Sheila G. [2] ; Silbiger, Vivian N. [1] ; Genvigir, Fabiana D. V. [1] ; Willrich, Maria Alice V. [1] ; Arazi, Simone S. [1] ; Luchessi, Andre D. [1] ; Hirata, Mario H. [1] ; Bernik, Marcia M. S. [3] ; Dorea, Egidio L. [3] ; Santos, Carla [4, 5] ; Faludi, Andre A. [6] ; Bertolami, Marcelo C. [6] ; Salas, Antonio [5] ; Freire, Ana [5] ; Lareu, Maria V. [5] ; Phillips, Christopher [5] ; Porras-Hurtado, Liliana [5] ; Fondevila, Manuel [5] ; Carracedo, Angel [5] ; Hirata, Rosario D. C. [1]
Total Authors: 22
Affiliation:
[1] Univ Sao Paulo, Fac Pharmaceut Sci, BR-05508900 Sao Paulo - Brazil
[2] Life Technol, BR-04311000 Sao Paulo - Brazil
[3] Univ Sao Paulo, Univ Hosp, BR-05508000 Sao Paulo - Brazil
[4] Univ Aveiro, Dept Biol, P-3810193 Aveiro - Portugal
[5] Univ Santiago de Compostela, Inst Legal Med, Forens Genet Unit, Galicia 15705 - Spain
[6] Dante Pazzanese Inst, BR-04012909 Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 12, n. 9, p. 5815-5827, SEP 2011.
Web of Science Citations: 40
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. (AU)

FAPESP's process: 08/06667-9 - Association study of 230 polymorphisms in 60 candidate genes and response to atorvastatin
Grantee:Rosario Dominguez Crespo Hirata
Support type: Regular Research Grants