[Association of a polymorphic marker Trp719Arg of KIF6 gene with effects of atorvastatin and simvastatin in patients with early ischemic heart disease]

Kardiologiia. 2011;51(9):4-12.
[Article in Russian]

Abstract

Action of statins is characterized by pronounced variability what is caused by effects of a multitude of factors. Main of these factors appears to be genetic peculiarity of patients. We studied influence of polymorphic marker Trp719Arg of KIF6 gene on lipid and nonlipid effects of atorvastatin and simvastatin. The studied genetic marker is associated with risk of development of ischemic heart disease and myocardial infarction as well as efficacy of therapy with statins according to data of a number of large multicenter studies. We examined 60 men with ischemic heart disease which had manifested in young age when genetic factors were most expressed and had special significance. Efficacy of 40 mg/day simvastatin did not depend on genotypes of polymorphic marker Trp719Arg of KIF6. Therapy with 10 mg/day atorvastatin was more effective in carriers of polymorphic marker Trp719Arg of KIF6 gene by action on dynamics of changes of high sensitivity C-reactive protein and dispersion of high density lipoprotein response. Increase of atorvastatin dose to 80 mg/day abolished influence of genotypes. Thus for the first time we discovered influence of polymorphic marker Trp719Arg of KIF6 gene on individual response to therapy with 10 mg/day of atorvastatin, while and apoA1, structural protein of high density lipoproteins can be considered as a marker of "fast response".

MeSH terms

  • Age of Onset
  • Apolipoprotein A-I / metabolism
  • Atorvastatin
  • C-Reactive Protein / metabolism
  • Dose-Response Relationship, Drug
  • Heptanoic Acids* / administration & dosage
  • Heptanoic Acids* / pharmacokinetics
  • Humans
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / pharmacokinetics
  • Kinesins / genetics*
  • Male
  • Middle Aged
  • Myocardial Ischemia* / drug therapy
  • Myocardial Ischemia* / epidemiology
  • Myocardial Ischemia* / genetics
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Pyrroles* / administration & dosage
  • Pyrroles* / pharmacokinetics
  • Simvastatin* / administration & dosage
  • Simvastatin* / pharmacokinetics
  • Treatment Outcome

Substances

  • Apolipoprotein A-I
  • Heptanoic Acids
  • Hypolipidemic Agents
  • Pyrroles
  • C-Reactive Protein
  • Atorvastatin
  • Simvastatin
  • KIF6 protein, human
  • Kinesins