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

Clin Chem Lab Med. 2012 Mar;50(3):441-8. doi: 10.1515/cclm.2011.804.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / pharmacology*
  • Anticholesteremic Agents / therapeutic use
  • Brazil
  • European Continental Ancestry Group / genetics*
  • Female
  • Gene Frequency / genetics
  • Haplotypes / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics*
  • Polymorphism, Single Nucleotide*
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use*
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Simvastatin