title: Possible gene-gender interaction between the SLCO1B1 polymorphism and statin treatment efficacy.
abstract: OBJECTIVE
  A significant inter-individual variability in statin treatment efficacy is likely to have a strong genetic background. A candidate gene with the potential to influence statin treatment efficacy is SLCO1B1. This gene codes for the solute carrier organic anion transporter, which has been shown to regulate the hepatic uptake of statins and some other drugs.
  
  
  METHODS
  The SLCO1B1 rs4149056 (T>C) polymorphism was successfully analysed in a group of 253 patients with dyslipidemia (treated with simvastin or atorvastatin, 10 or 20 mg per day) and 470 healthy normolipidemic controls. The polymorphism was analysed using nested PCR-RFLP. Lipid levels (total, LDL and HDL cholesterol; triglycerides) were analysed before and after 10-13 weeks of treatment.
  
  
  RESULTS
  After treatment, as expected, there was a significant decrease both in the total cholesterol (7.60±1.36 → 5.37±1.12 mmol/L, p<0.001) and LDL cholesterol (5.04±1.34 → 3.17±0.99 mmol/L, p<0.001) levels. The distribution of the individual genotypes in the patients (TT=61.7%, CT=31.6%, CC=6.7%) was similar (p=0.35) to that of the normolipidemic controls (TT=64.4%, CT=31.3%, CC=4.3%). Homozygous CC males exhibited the lowest (Δ -21.2±7.2%) decrease of total cholesterol in contrast to the females, in whom the same genotype was associated with the highest (Δ -33.5±7.6 %) decrease (p=0.04 for gene-gender interaction).
  
  
  CONCLUSIONS
  The results of our pilot study suggest possible gender-dependent effects of the rs4149056 variant within the SLCO1B1 gene on statin treatment efficacy.
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jahb@ikem.cz
authors.forename: Jaroslav A
authors.initials: JA
authors.lastname: Hubacek
authors.forename: Dana
authors.initials: D
authors.lastname: Dlouha
authors.forename: Vera
authors.initials: V
authors.lastname: Adámkova
authors.forename: Vera
authors.initials: V
authors.lastname: Lanska
authors.forename: Richard
authors.initials: R
authors.lastname: Ceska
authors.forename: Michal
authors.initials: M
authors.lastname: Vrablik
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D050171:Dyslipidemias / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006538:Heptanoic Acids / Q000008:administration & dosage; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D012737:Sex Factors; D019821:Simvastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011758:Pyrroles; C503999:SLCO1B1 protein, human; D014280:Triglycerides; D000069059:Atorvastatin; D019821:Simvastatin