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Impact of interleukin-10 gene polymorphisms on tacrolimus dosing requirements in Chinese liver transplant patients during the early posttransplantation period

European Journal of Clinical Pharmacology volume 67, pages 803–813 (2011)Cite this article

Abstract

Aim

Pharmacogenetics holds the potential to elucidate the inherited basis of differences between individual responses to drugs. Impacts of CYP3A5 and ABCB1 gene polymorphisms on the immunosuppressant tacrolimus have been reported in previous studies of liver transplantation. The functions of interleukin-10 (IL-10) gene expression are complex in the early period after liver transplantation. In this study, we examined the IL-10 genotypes of both recipients and donors to clarify the influence of these genetic variants on tacrolimus dose requirements and pharmacokinetics.

Methods

Genetic polymorphisms of IL-10, CYP3A5, and ABCB1 were evaluated for 53 liver transplant recipients and 53 donors. Tacrolimus doses and blood concentrations were determined at 1, 2, and 3 weeks, and 1 month after transplantation. IL-10 polymorphisms at G-1082A, C-819 T, and C-592A; CYP3A5 polymorphisms at A6986G; and ABCB1 polymorphisms at C1236T, G2677T, and C3435T were assessed by PCR amplification and DNA sequencing.

Results

Recipients who received organs from CYP3A5*3/*3 donors had higher tacrolimus C/D ratios. In the first 2 weeks, the tacrolimus C/D ratios of the recipients with donors who were CYP3A5 nonexpressors and had a low IL-10 production genotype (-819TT, -592 AA) were higher than those with donors who were CYP3A5 nonexpressors and had a high IL-10 production genotype (-819CC or CT, -592CC or AC). There were no significant differences in laboratory data or clinical characteristics (which could influence the tacrolimus C/D ratio) between the two groups of patients (P > 0.05).

Conclusion

Determining IL-10 and CYP3A5 polymorphisms of donors may allow individualized tacrolimus dosage regimens to be determined for liver transplant patients during the early posttransplantation period.

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Abbreviations

CYP3A5:

Cytochrome P450

ABCB1:

ATP-binding cassette subfamily B, member 1

IL-10:

Interleukin-10

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Acknowledgments

This research was supported by Leading Project of Science and Technology Commission of Shanghai Municipality (074119605); the Program for Outstanding Medical Academic Leader of Shanghai Municipality (LJ06024); and National Key Technology R&D Program in the 11th Five Year Plan of China (2008BAI60B03).

Author information

Affiliations

  1. Department of Pharmacy, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, 200080, China

    Xiaoqing Zhang & Gaolin Liu

  2. Department of Hepatobiliary Pancreatic Surgery, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, 200080, China

    Zhaowen Wang, Junwei Fan & Zhihai Peng

  3. Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China

    Xiaoqing Zhang

Authors
  1. Xiaoqing Zhang
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  2. Zhaowen Wang
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  3. Junwei Fan
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  4. Gaolin Liu
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  5. Zhihai Peng
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Corresponding authors

Correspondence to Gaolin Liu or Zhihai Peng.

Additional information

Zhang Xiaoqing and Wang Zhaowen contributed equally to this work.

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Zhang, X., Wang, Z., Fan, J. et al. Impact of interleukin-10 gene polymorphisms on tacrolimus dosing requirements in Chinese liver transplant patients during the early posttransplantation period. Eur J Clin Pharmacol 67, 803–813 (2011). https://doi.org/10.1007/s00228-011-0993-8

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Keywords

  • Interleukin-10
  • Gene polymorphism
  • Tacrolimus
  • Liver transplantation