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Effects of ABCG2 and SLCO1B1 gene variants on inflammation markers in patients with hypercholesterolemia and diabetes mellitus treated with rosuvastatin

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

Dysregulation of angiogenesis and inflammation play important roles in the development of atherosclerosis. Rosuvastatin (RST) was widely used in atherosclerosis therapy. Genetic variations of transporters may affect the rosuvastatin concentration in plasma and reflect different clinical treatment. The aim of this study was to explore the drug transport related single-nucleotide polymorphisms (SNPs) on RST pharmacokinetic and the further on pro-angiogenic and pro-inflammatory factors.

Methods

A total of 269 Chinese patients with hypercholesterolemia and diabetes mellitus were enrolled. They were treated with RST to lower cholesterol. The plasma concentration of RST was determined using a validated UPLC-MS/MS method. Seven single-nucleotide polymorphisms (SNPs) in six genes were genotyped using the Sanger dideoxy DNA sequencing method. The serum concentrations of inflammation markers were determined using ELISA kits.

Results

ABCG2 421C > A (rs2231142) and SLCO1B1 521 T > C (rs4149056) variations were highly associated with plasma concentrations of RST (P < 0.01, FDR < 0.05). The serum MCP-1, sVCAM-1, and TNF-α levels were significantly different between the ABCG2 421C > A and SLCO1B1 521 T > C genetic variation groups (P < 0.01). RST concentration was negatively correlated with sVCAM-1 concentration (r = 0.150, P = 0.008).

Conclusion

ABCG2 421C > A (rs2231142) and SLCO1B1 521 T > C (rs4149056) genetic variants affect RST concentration significantly and potentially affect serum levels of pro-inflammatory and pro-angiogenic markers. The effects on anti-inflammation might not be related to high plasma exposure of RST.

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Funding

This study was supported by the National Natural Science Foundation of China (Grant no. 81503339).

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Authors and Affiliations

  1. Department of Pharmacy, China-Japan Friendship Hospital, Beijing, 100029, China

    Dan Zhang, Yangming Ding, Xiaoxue Wang, Wenwen Du, Wenqian Chen, Xianglin Zhang & Pengmei Li

  2. Department of Pharmacology, School of Pharmacy, Binzhou Medical University, Yantai, 264003, China

    Wenyu Xin

Authors
  1. Dan Zhang
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  2. Yangming Ding
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  3. Xiaoxue Wang
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  4. Wenyu Xin
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  5. Wenwen Du
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  6. Wenqian Chen
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  7. Xianglin Zhang
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  8. Pengmei Li
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Contributions

DZ: analyzed data and wrote the manuscript. YMD, XXW, WYX, WWD and WQC: contributed to the development, interpretation of results. XLZ and PML revision of the manuscript.

Corresponding author

Correspondence to Pengmei Li.

Ethics declarations

The protocol for study was approved by the Bioethical Committee of China-Japan Friendship Hospital and all the participants gave informed consent.

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The authors declare that they have no conflict of interest.

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Zhang, D., Ding, Y., Wang, X. et al. Effects of ABCG2 and SLCO1B1 gene variants on inflammation markers in patients with hypercholesterolemia and diabetes mellitus treated with rosuvastatin. Eur J Clin Pharmacol 76, 939–946 (2020). https://doi.org/10.1007/s00228-020-02882-4

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  • DOI: https://doi.org/10.1007/s00228-020-02882-4

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