Effects of polymorphisms in ABCG2, SLCO1B1, SLC10A1 and CYP2C9/19 on plasma concentrations of rosuvastatin and lipid response in Chinese patients

Pharmacogenomics. 2013 Aug;14(11):1283-94. doi: 10.2217/pgs.13.115.

Abstract

Aim: This study examined whether the ABCG2 421C>A polymorphism and variants in other genes potentially related to the pharmacokinetics of rosuvastatin influenced the plasma concentration of rosuvastatin in Chinese patients with hypercholesterolemia.

Patients & methods: Overnight fasting blood samples were collected from 291 patients who had received a rosuvastatin 10 mg night-time dose for at least 4 weeks. Plasma concentrations of rosuvastatin and N-desmethyl rosuvastatin were quantified using liquid chromatography tandem mass spectrometry.

Results: In subjects with the ABCG2 421AA genotype (n = 39), the mean plasma concentrations of rosuvastatin and its metabolite were 63 and 41% greater than the values in those with the 421CA genotype (n = 108) and 120 and 99% greater than in those with the 421CC genotype (n = 129). The plasma concentrations of rosuvastatin were associated (r = -0.194; p = 0.001) with the percentage reduction in low-density lipoprotein cholesterol with rosuvastatin, but the association was not significant after adjusting for the ABCG2 421C>A polymorphism. The SLCO1B1 521T>C polymorphism was associated with increased plasma concentrations of rosuvastatin and impaired N-demethylation of rosuvastatin, but had no impact on its lipid-lowering effect. Polymorphisms in CYP2C9, CYP2C19 and SLC10A1 had minimal effects.

Conclusion: These findings suggest that the increased plasma concentrations of rosuvastatin in Chinese patients are associated with increased lipid-lowering effects and lower doses of rosuvastatin should be effective in subjects with the ABCG2 421C>A variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Aged
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian Continental Ancestry Group / genetics
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / genetics
  • Cytochrome P-450 CYP2C9
  • Female
  • Fluorobenzenes / administration & dosage*
  • Fluorobenzenes / blood
  • Fluorobenzenes / pharmacokinetics
  • Genetic Association Studies
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Pyrimidines / administration & dosage*
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics
  • Rosuvastatin Calcium
  • Sulfonamides / administration & dosage*
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics
  • Symporters / genetics*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Cholesterol, LDL
  • Fluorobenzenes
  • Liver-Specific Organic Anion Transporter 1
  • Neoplasm Proteins
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Dependent
  • Pyrimidines
  • SLCO1B1 protein, human
  • Sulfonamides
  • Symporters
  • sodium-bile acid cotransporter
  • Rosuvastatin Calcium
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases