title: The effect of statin therapy on plasma high-density lipoprotein cholesterol levels is modified by paraoxonase-1 in patients with familial hypercholesterolaemia.
abstract: OBJECTIVE
  Statins reduce low-density lipoprotein cholesterol (LDL-C) and can raise high-density lipoprotein cholesterol (HDL-C). HDL-bound paraoxonase-1 (PON1) is associated with variations in plasma HDL-C, and may, therefore, contribute to changes of HDL-C during statin therapy.
  
  
  METHODS
  The effects of baseline PON1 status to HDL-C changes because of statin therapy were investigated. PON1 status was determined with (i) PON1 -107C>T and 192Q>R genotype, (ii) PON1 levels and (iii) PON1 paraoxonase, diazoxonase and arylesterase activity.
  
  
  METHODS
  Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
  
  
  METHODS
  A total of 134 familial hypercholesterolaemia (FH) patients undergoing atorvastatin or simvastatin therapy.
  
  
  RESULTS
  PON1 levels and activities significantly modified the HDL-C increment (P=0.002 for PON1 levels and arylesterase activity and P=0.001 for diazoxonase activity). The effects were even more evident amongst subgroup classifications based on PON1 status and baseline HDL-C concentrations: the HDL-C increment was more pronounced in subgroups of -107CT/TT or 192QR/RR genotype combined with low baseline HDL-C (+13.9%, P<0.001, respectively+15.4%, P<0.001). In contrast, the -107CC or 192QQ genotype in combination with high baseline HDL-C, did not show a significant increase of HDL-C.
  
  
  CONCLUSIONS
  PON1 status in conjunction with baseline HDL-C levels predicts HDL-C increment during statin therapy in FH patients.
authors.affiliation: Research Laboratory of the Department of Clinical Chemistry, University Medical Centre Utrecht, Utrecht, the Netherlands. t.m.vanhimbergen@azu.nl
authors.forename: T M
authors.initials: TM
authors.lastname: Himbergen
authors.forename: L J H
authors.initials: LJ
authors.lastname: van Tits
authors.forename: H A M
authors.initials: HA
authors.lastname: Voorbij
authors.forename: J
authors.initials: J
authors.lastname: de Graaf
authors.forename: A F H
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: M
authors.initials: M
authors.lastname: Roest
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics; D000069059:Atorvastatin; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase