Lipid-lowering response to statins is affected by CYP3A5 polymorphism

Pharmacogenetics. 2004 Aug;14(8):523-5. doi: 10.1097/01.fpc.0000114762.78957.a5.


Individuals expressing the polymorphic CYP3A5 enzyme might show a more than average efficiency in the metabolism of lovastatin, simvastatin and atorvastatin. We studied whether the expression of CYP3A5 is associated with an impaired lipid-lowering response to statins in 69 Caucasian patients. Lovastatin, simvastatin and atorvastatin were significantly less effective in CYP3A5 expressors than in non-expressors. The mean serum total cholesterol concentration at 1 year was 23% higher (P = 0.0014) and the mean serum low-density lipoprotein cholesterol concentration was 24% higher (P = 0.036) in subjects possessing the CYP3A5*1 allele (CYP3A5 expressors, n = 7) than in subjects homozygous for the CYP3A5*3 allele (non-expressors, n = 39). The mean percentage reduction in serum total cholesterol from baseline was significantly smaller in CYP3A5 expressors than in non-expressors (17% versus 31%, P = 0.026). No association between hypolipidemic efficacy and CYP3A5 polymorphism was observed among 23 subjects taking statins that are not dependent on CYP3A5 (fluvastatin, pravastatin). These findings suggest that CYP3A5 may be a genetic determinant of interindividual differences in response to certain statins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / pharmacology*
  • Atorvastatin
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Genotype
  • Heptanoic Acids / pharmacology
  • Homozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Lovastatin / pharmacology
  • Male
  • Polymorphism, Genetic / genetics*
  • Pyrroles / pharmacology
  • Simvastatin / pharmacology


  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • CYP3A protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A