title: SLCO1B1 gene variability influences lipid-lowering efficacy on simvastatin therapy in Southern Brazilians.
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.
authors.affiliation: Departamento de Genética, Universidade Federal do RioGrande do Sul, Porto Alegre, Brazil.
authors.forename: Vinicius A
authors.initials: VA
authors.lastname: Sortica
authors.forename: Marilu
authors.initials: M
authors.lastname: Fiegenbaum
authors.forename: Luciana O
authors.initials: LO
authors.lastname: Lima
authors.forename: Cézar R
authors.initials: CR
authors.lastname: Van der Sand
authors.forename: Luis C
authors.initials: LC
authors.lastname: Van der Sand
authors.forename: Maria E W
authors.initials: ME
authors.lastname: Ferreira
authors.forename: Renan C
authors.initials: RC
authors.lastname: Pires
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001938:Brazil; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics*
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D019821:Simvastatin