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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 12, n. 9, p. 5815-5827, SEP 2011.
• Citações Web of Science: 40

Resumo

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)

• Processo FAPESP: 08/06667-9 - Estudo de associação entre 230 polimorfismos em 60 genes candidatos e a resposta a atorvastatina
• Beneficiário: Rosario Dominguez Crespo Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Regular