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The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients

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A Correction to this article was published on 24 March 2022

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Abstract

Background

The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C0/D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients.

Methods

Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C0/D at 5, 10, 15, and 30 days after transplantation.

Results

Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C0/D than those with the TC/CC genotype (p < 0.05). Additionally, the TAC C0/D values of recipients with the capacity for low IL-10 activity (-819 TT) engrafted with CYP3A5 non-expressers were higher compared to the intermediate/high activity of IL-10 -819C > T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p < 0.05).

Conclusions

Genetic polymorphisms of IL-10 -819C > T and CYP3A5 6986A > G influence the TAC C0/D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period.

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Acknowledgements

This work was supported by the China Post doctoral Science Foundation (NO: 2019M662207), Anhui Natural Science Fund Project (1908085QH363).

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  1. Zhaolin Chen, Xi Cheng have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Hospital, Hefei, Anhui, 230001, P.R. China

    Zhaolin Chen, Xi Cheng, Liqin Tang, Yan Fang, Hongxiao Chen, Lei Zhang & Aizong Shen

  2. Department of Data & Analytics, WuXi Diagnostics Limited Corporation, Shanghai, 200131, People’s Republic of China

    Liwen Zhang

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  1. Zhaolin Chen
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Chen, Z., Cheng, X., Zhang, L. et al. The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients. Pharmacol. Rep 73, 1418–1426 (2021). https://doi.org/10.1007/s43440-021-00288-2

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