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

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.

• Authors: Hon-Kit Lee, Miao Hu, Sandra Sh Lui, Chung-Shun Ho, Chun-Kwok Wong, Brian Tomlinson
• Journal: Pharmacogenomics (Pharmacogenomics) Vol. 14 Issue 11 Pg. 1283-94 (Aug 2013) ISSN: 1744-8042 [Electronic] England
• PMID: 23930675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (genetics)
• Adult
• Aged
• Aryl Hydrocarbon Hydroxylases (genetics)
• Asian People (genetics)
• Cholesterol, LDL (blood, genetics)
• Cytochrome P-450 CYP2C9
• Female
• Fluorobenzenes (administration & dosage, blood, pharmacokinetics)
• Genetic Association Studies
• Humans
• Lipid Metabolism (drug effects, 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, blood, pharmacokinetics)
• Rosuvastatin Calcium
• Sulfonamides (administration & dosage, blood, pharmacokinetics)
• Symporters (genetics)