European Journal of Clinical Pharmacology

, Volume 60, Issue 12, pp 843–848 | Cite as

Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients

  • An Wang
  • Bang-Ning Yu
  • Chen-Hui Luo
  • Zhi-Rong Tan
  • Gan Zhou
  • Lian-Sheng Wang
  • Wei Zhang
  • Zhi Li
  • Jie Liu
  • Hong-Hao ZhouEmail author



To determine the frequencies of CYP3A4 alleles (CYP3A4*4,*5 and *6) in Chinese hyperlipidemic patients and to observe the impact of CYP3A4*4 (Ile118Val) genetic polymorphism on the lipid-lowering effects of simvastatin and on the activity of CYP3A4.


From hospitalized and non-hospitalized patients, 211 unrelated hyperlipidemic patients were recruited for genotyping. CYP3A4 genotypes were determined by means of polymerase chain reaction and restriction fragment length polymorphism analysis. Of the non-hospitalized hyperlipidemic patients, 8 with CYP3A4*1/*1 and 8 with CYP3A4*1/*4 genotypes were selected to be treated with 20 mg simvastatin daily for 4 weeks. Serum triglycerides (TG), cholesterol (CHO) and low-density lipoprotein (LDL) levels were determined using an automated analyzer (Hitachi 747, Boehringer Mannheim, Mannheim, Germany). CYP3A4 activity was determined by the ratio of 6-hydroxycortisol to free cortisol (6-OHC/FC) in the morning spot urine with a high-throughput liquid chromatography–tandem mass spectrometry method.


Of 211 subjects, 14 (allele frequency 3.32%) were heterozygous for CYP3A4*4 (Ile118Val). Nevertheless, no subjects with a CYP3A4*5 or CYP3A4*6 allele or homozygous for CYP3A4*4 were identified. The ratio of 6β-OHC/FC was 9.9±13.7 and 56.6±35.7 in subjects with the Ile118Val variant (n=8) and in CYP3A4 wild-type subjects (n=8), respectively (P=0.0039). After oral intake of simvastatin 20 mg daily for 4 weeks, the change of serum lipids in CYP3A4*1/*1 and CYP3A4*1/*4 groups showed a significant difference, with a mean decrease in triglycerides and total cholesterol of 38.1±7.6% versus 25.1±8.3% (P=0.034) and of 35.8±9.6% versus 22.0±20.4% (P=0.0015) (means ± SD), respectively. We found no statistically significant difference in the reductions of LDL between subjects carrying the *1 and *4 genotypes (29.0±7.4% versus 36.8±8.8%, P=0.0721).


The allele frequency of CYP3A4*4 was 3.32% among the hyperlipidemic patients from the Chinese mainland. CYP3A4*4 was an allelic variant related to a functional decrease of CYP3A4 activity, and *4 expression seemed to increase the lipid-lowering effects of simvastatin.


Simvastatin Felodipine CYP3A4 Activity Hyperlipidemic Patient CYP2D6 Polymorphism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



All authors have no conflict of interest. A project supported by the National Science Foundation of China grants F30130210.


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • An Wang
    • 1
    • 2
  • Bang-Ning Yu
    • 1
  • Chen-Hui Luo
    • 1
  • Zhi-Rong Tan
    • 1
  • Gan Zhou
    • 1
  • Lian-Sheng Wang
    • 1
  • Wei Zhang
    • 1
  • Zhi Li
    • 1
  • Jie Liu
    • 1
  • Hong-Hao Zhou
    • 1
    Email author
  1. 1.Pharmacogenetics Research Institute, Institute of Clinical PharmacologyCentral South UniversityChangshaChina
  2. 2.Department of Health Toxicology, School of Public HealthCentral South UniversityChangshaChina

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