Research Article

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

Department of Medicine & Therapeutics, The Chinese University of Kong Kong, Shatin, Hong Kong SAR, China

Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China

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Miao Hu

Department of Medicine & Therapeutics, The Chinese University of Kong Kong, Shatin, Hong Kong SAR, China

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Sandra SH Lui

Department of Medicine & Therapeutics, The Chinese University of Kong Kong, Shatin, Hong Kong SAR, China

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Chung-Shun Ho

Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China

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Chun-Kwok Wong

Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China

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Brian Tomlinson

* Author for correspondence

Department of Medicine & Therapeutics, The Chinese University of Kong Kong, Shatin, Hong Kong SAR, China.

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Email the corresponding author at btomlinson@cuhk.edu.hk

Published Online:9 Aug 2013https://doi.org/10.2217/pgs.13.115

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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.

Original submitted 18 April 2013; Revision submitted 17 June 2013

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Vol. 14, No. 11

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Published online 9 August 2013

Published in print August 2013

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Acknowledgements

The authors would like to thank E Chau for her assistance in patient recruitment and E Poon for her help with the DNA extraction and genotyping polymorphisms.

Financial & competing interests disclosure

The work described in this paper was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. CUHK 4472/06M). This funding source had no role in the conduct of the study. B Tomlinson has received research funding to perform clinical studies from Abbott Laboratories Ltd, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck Serono, Merck Sharp and Dohme, Novartis, Roche and Takeda, and has acted as a consultant or speaker on occasions for Amgen, AstraZeneca, Boehringer Ingelheim, Genzyme, Janssen, Merck Serono, Merck Sharp and Dohme, Ranbaxy and Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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