title: The human paraoxonase-1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters.
abstract: OBJECTIVE
  Human serum paraoxonase-1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low-density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters.
  
  
  METHODS
  One hundred and sixty-four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day(-1) atorvastatin, 10/20 mg day(-1) simvastatin and 80 mg day(-1) extended-release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method.
  
  
  RESULTS
  Three months of statin treatment significantly increased paraoxonase activity in every statin-treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin-treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group.
  
  
  CONCLUSIONS
  The PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.
authors.affiliation: First Department of Medicine, University of Debrecen Medical and Health Science Centre, Debrecen, Hungary.
authors.forename: Hossein Z
authors.initials: HZ
authors.lastname: Mirdamadi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sztanek
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Derdak
authors.forename: Ildiko
authors.initials: I
authors.lastname: Seres
authors.forename: Mariann
authors.initials: M
authors.lastname: Harangi
authors.forename: György
authors.initials: G
authors.lastname: Paragh
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics / Q000627:therapeutic use*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000235:genetics; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics; D007211:Indoles / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D011758:Pyrroles; D000077340:Fluvastatin; D000069059:Atorvastatin; D019821:Simvastatin; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human