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A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform

The Pharmacogenomics Journal volume 17, pages 174–179 (2017)Cite this article

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A Corrigendum to this article was published on 13 December 2016

Abstract

Genetic association studies on the pharmacokinetics of tacrolimus have reported conflicting results, except for the role of the CYP3A5*3 polymorphism. The objective of this study was to identify genetic variants affecting the pharmacokinetics of tacrolimus using the DMETTM Plus microarray in 42 healthy males. Aside from CYP3A5*3, the rs3814055 polymorphism in the NR1I2 gene was associated with the tacrolimus pharmacokinetics based on false discovery rate-corrected multiple tests and the least absolute shrinkage and selection operator analysis. The area under the concentration-time curve to the last quantifiable time point (AUClast) was 3.42 times greater in subjects with homozygous mutations in both genes (CYP3A5*3/*3 and NR1I2 T/T) than in wild-type subjects. The two variants explained the 54% variability in the tacrolimus AUClast. An in vitro luciferase reporter assay indicated that downregulation of PXR expression is the likely molecular mechanism responsible for the increased exposure to tacrolimus in subjects carrying the rs3814055 C>T variant.

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Acknowledgements

This study was sponsored by a research grant from Chong Kun Dang Pharmaceutical, Seoul, Korea, and by a research grant for new faculty settlement, Seoul National University, Seoul, Korea.

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Author notes

  1. Y Choi and F Jiang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea

    Y Choi, F Jiang, H An & H Lee

  2. Department of Statistics, Seoul National University, Seoul, Korea

    H An

  3. Department of Pharmacology, Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul, Korea

    H J Park & J H Choi

  4. Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

    H Lee

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  1. Y Choi
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Correspondence to H Lee.

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Choi, Y., Jiang, F., An, H. et al. A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform. Pharmacogenomics J 17, 174–179 (2017). https://doi.org/10.1038/tpj.2015.99

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