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Clinical Chemistry and Laboratory Medicine (CCLM)

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SLCO1B1 gene variability influences lipid-lowering efficacy on simvastatin therapy in Southern Brazilians

Vinicius A. Sortica1 / Marilu Fiegenbaum2 / Luciana O. Lima2 / Cézar R. Van der Sand3 / Luis C. Van der Sand3 / Maria E.W. Ferreira3 / Renan C. Pires3 / 1

1Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

2Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil

3Centro de Diagnóstico Cardiológico, Porto Alegre, Brazil

Corresponding author: Professor Mara H. Hutz, Departamento de Genética, Instituto de Biociências, UFRGS, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil Phone: +55 51 3316-6720, Fax: +55 51 3316-7311

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 50, Issue 3, Pages 441–448, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/cclm.2011.804, March 2012

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Background:Variants in uptake and efflux transporters can influence diverse statin pharmacokinetics in different populations. This study aimed to investigate the influence of SLCO1B1 gene polymorphism on simvastatin treatment efficacy in a Brazilian population of European ancestry.

Methods: Two hundred and sixteen hypercholesterolemic patients were treated with 20 mg/day simvastatin for 6 months. Plasma lipid and lipoprotein levels were measured at baseline and after 2 and 6 months of treatment. The single nucleotide polymorphisms (SNPs) c.388A>G, c.463C>A and c.521T>C at SLCO1B1 gene were determined by allelic discrimination with TaqMan 5'-nuclease assays. The 388G allele was observed in 160 patients, the 521 C allele was observed in 64 individuals, whereas 61 subjects were 463 A allele carriers.

Results: Carriers of the SLCO1B1 388G allele had a greater reduction of total cholesterol and LDL cholesterol with simvastatin treatment, when compared with 56 388A homozygotes (–28.8% vs. –15.8%, p=0.005 and –39.0% vs. –30.6%, p=0.003; respectively). The c.463C>A and c.521T>C SNPs were not associated with simvastatin treatment. The SLCO1B1 haplotypes showed no statistically significant differences in mean percentage reductions in lipid and lipoprotein levels after simvastatin treatment.

Conclusions: The present study suggests that the SLCO1B1 c.388A>G polymorphism could play a role in the inter-individual variation of clinical response to simvastatin in Brazilians. These results add to those that suggest that the effects of SLCO1B1 variants may be statin specific.

Keywords: OATP1B1; SLCO1B1; simvastatin; pharmaco­genetics

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