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

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.