CYP3A4*1G polymorphism is associated with lipid-lowering efficacy of atorvastatin but not of simvastatin

Eur J Clin Pharmacol. 2008 Sep;64(9):877-82. doi: 10.1007/s00228-008-0502-x. Epub 2008 Jun 5.

Abstract

Purpose: Our aim was to observe the impact of CYP3A4*1G genetic polymorphism on lipid-lowering efficacy of statins.

Methods: We studied 217 unrelated hyperlipidemic patients who prospectively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy (20 mg day(-1) p.o.) for 4 weeks. Genotyping of CYP3A4*1G was conducted by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were determined before and after treatment by enzymatic assays.

Results: The frequency of CYP3A4*1G in Chinese hyperlipidemic patients was 0.276. After atorvastatin treatment, the mean percentage reduction in serum TC was 16.8 +/- 3.3% (*1/*1), 17.8 +/- 3.8% (*1/*1G), and 20.9 +/- 5.0% (*1G/*1G), respectively. The CYP3A4*1G polymorphism had a gene-dose-dependent effect on percentage reduction in serum TC (P < 0.01). Conversely, there was no significant association between lipid-lowering efficacy of simvastatin and CYP3A4*1G polymorphism.

Conclusions: Carrying CYP3A4*1G increase the lipid-lowering efficacy of atorvastatin and may have no significant effect on simvastatin treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anticholesteremic Agents / therapeutic use*
  • Asian People / genetics
  • Atorvastatin
  • Cholesterol, LDL / blood
  • Cytochrome P-450 CYP3A / genetics*
  • Female
  • Gene Frequency
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Simvastatin / therapeutic use*

Substances

  • Anticholesteremic Agents
  • Cholesterol, LDL
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin
  • Simvastatin
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human