CYP2C9 Genetic Polymorphism is a Potential Predictive Marker for the Efficacy of Rosuvastatin Therapy

Clin Lab. 2015;61(9):1317-24. doi: 10.7754/clin.lab.2015.150123.

Abstract

Background: There is well-known inter-individual variability in the cholesterol-lowering effect of statins. However, inter-individual variability in response to rosuvastatin treatment in subjects with hypercholesterolemia has not been clearly established. This study aimed to evaluate the associations of CYP2C9 genetic polymorphism with the efficacy and safety of rosuvastatin in Chinese patients with hyperlipidemia.

Methods: A total of 218 patients with hyperlipidemia were selected and treated with 10 mg rosuvastatin per day for 12 weeks. Blood samples were collected prior to the treatment and after 4, 8, and 12 weeks of treatment. Clinical biochemistry analyses for serum lipid profiles were performed. Genotyping for CYP2C9 polymorphisms was performed using allele-specific real-time PCR.

Results: 197 out of 218 patients featured a wild-type CYP2C9*1/*1 genotype, and 21 patients featured a CYP2C9*1/*3 or CYP2C9*3/*3 mutation genotype. No patients with CYP2C9*2 alleles were identified. Sixteen patients discontinued the medication due to adverse effects. No serious adverse events (i.e., hepatotoxicity or myolysis) were observed. After the 12 weeks of treatment, we observed significant reductions in total cholesterol (TC), triglycerides and low-density lipoprotein (LDL) levels compared to baseline (p < 0.05). Patients with the mutant genotype showed a higher TC-lowering and LDL-lowing effect compared to those with wild-type genotypes (TC: 45.05% vs. 38.96%, p = 0.041; LDL: 44.97% vs. 39.28%, p = 0.029). The frequency of adverse drug reactions in the studied patients did not differ by CYP2C9 genotypes (p > 0.05).

Conclusions: This study suggests that the CYP2C9 polymorphism may be involved in the lipid-lowering efficacy of rosuvastatin in patients with hyperlipidemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People / genetics*
  • China
  • Cholesterol / blood
  • Cholesterol, LDL / blood
  • Combined Modality Therapy
  • Cytochrome P-450 CYP2C9 / genetics*
  • Cytochrome P-450 CYP2C9 / physiology
  • Diet, Fat-Restricted
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperlipidemias / blood
  • Hyperlipidemias / diet therapy
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / enzymology
  • Hyperlipidemias / genetics
  • Inactivation, Metabolic / genetics
  • Individuality
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Real-Time Polymerase Chain Reaction
  • Rosuvastatin Calcium / pharmacokinetics
  • Rosuvastatin Calcium / therapeutic use*

Substances

  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Rosuvastatin Calcium
  • Cholesterol
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9