title: Impact of CYP3A5 Gene Polymorphism on Efficacy of Simvastatin.
abstract: BACKGROUND
  One of the promises of human genetics is individualized therapy. Therefore, we evaluated the impact of CYP3A5 gene polymorphism on the effectiveness of simvastatin (a HMG-CoA reductase inhibitor).
  
  
  METHODS
  Patients (n = 191) with hypercholesterolemia were treated with simvastatin for at least 6 months and were genotyped for the CYP3A5 polymorphism.
  
  
  RESULTS
  The frequency of CYP3A5 polymorphism was 0.5% for WT (wild-type), 15.6% for HT (heterozygous, expressors) and 83.9% for HM (homozygous, non-expressors). Differences in lipid profile before and after dose-response of simvastatin treatment were described as % difference {[(variable after-variable before)/variable before]*100}. There was a trend towards the decrease of low density lipoprotein cholesterol (LDL-C) in HT individuals who had a -35.2% reduction with a dose of 20 mg simvastatin and HM individuals who had a slightly higher decrease (-37.5%) despite the lower dose of simvastatin (10 mg, p = 0.07). Furthermore, HT genotype individuals had significantly higher than expected (6-8%) LDL-C % difference between 20 and 40 mg of simvastatin (-35.2 vs -49.2%, p = 0.037). In individuals with HM genotype a significant LDL-C % difference was found between 10 and 40 mg of simvastatin (-37.5 vs -48.4%, p = 0.023).
  
  
  CONCLUSIONS
  The individuals with HM polymorphism display a trend towards higher LDL-C reductions compared with HT polymorphism. Within the same genotype, differences between doses were also observed. These findings need to be confirmed in larger studies.
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
authors.forename: Genovefa
authors.initials: G
authors.lastname: Kolovou
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
authors.forename: Georgia
authors.initials: G
authors.lastname: Ragia
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece; ; Molecular Immunology Laboratory, Onassis Cardiac Surgery Center Athens, Greece;
authors.forename: Vana
authors.initials: V
authors.lastname: Kolovou
authors.affiliation: Internal Medicine Department, Kimi General Hospital, Kimi, Greece;
authors.forename: Constantinos
authors.initials: C
authors.lastname: Mihas
authors.affiliation: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Katsiki
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vasiliadis
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
authors.forename: Sophie
authors.initials: S
authors.lastname: Mavrogeni
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Vartela
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center Athens, Greece;
authors.forename: Anna
authors.initials: A
authors.lastname: Tavridou
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
keywords: CYP3A5 gene polymorphism; Simvastatin; low density lipoprotein cholesterol.