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The Impact of Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid: Systematic Review and Meta-analysis

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Abstract

Background

Mycophenolic acid (MPA) is among the most commonly prescribed medications for immunosuppression following organ transplantation. Highly variable MPA exposure and drug response are observed among individuals receiving the same dosage of the drug. Identification of candidate genes whose polymorphisms could be used to predict MPA exposure and clinical outcome is of clinical value.

Objectives

This study aimed to determine the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of MPA in humans by means of a systematic review and meta-analysis.

Methods

A systematic search was conducted on PubMed, EMBASE, Web of Sciences, Scopus, and the Cochrane Library databases. A meta-analysis was conducted to determine any associations between genetic polymorphisms and pharmacokinetic or pharmacodynamic parameters of MPA. Pooled-effect estimates were calculated by means of the random-effects model.

Results

A total of 37 studies involving 3844 individuals were included in the meta-analysis. Heterozygous carriers of the UGT1A9 -275T>A polymorphism were observed to have a significantly lower MPA exposure than wild-type individuals. Four single nucleotide polymorphisms (SNPs), namely UGT1A9 -2152C>T, UGT1A8 518C>G, UGT2B7 211G>T, and SLCO1B1 521T>C, were also significantly associated with altered MPA pharmacokinetics. However, none of the investigated SNPs, including SNPs in the IMPDH gene, were found to be associated with the clinical efficacy of MPA. The only SNP that was associated with adverse outcomes was SLCO1B3 344T>G.

Conclusions

The present systematic review and meta-analysis identified six SNPs that were significantly associated with pharmacokinetic variability or adverse effects of MPA. Our findings represent the basis for future research and clinical implications with regard to the role of pharmacogenetics in MPA pharmacokinetics and drug response.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Sriphoom, Muang, Chiang Mai, 50200, Thailand

    Mingkwan Na Takuathung, Wannachai Sakuludomkan & Nut Koonrungsesomboon

  2. Musculoskeletal Science and Translational Research (MSTR) Center, , Chiang Mai University, Muang, Chiang Mai, Thailand

    Nut Koonrungsesomboon

Authors
  1. Mingkwan Na Takuathung
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  2. Wannachai Sakuludomkan
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  3. Nut Koonrungsesomboon
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Correspondence to Nut Koonrungsesomboon.

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Funding

This work was supported by a grant from the Faculty of Medicine, Chiang Mai University (No. 047-2564) and the Health Systems Research Institute.

Conflict of interest

Mingkwan Na Takuathung, Wannachai Sakuludomkan, and Nut Koonrungsesomboon have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

The Research Ethics Committee of the Faculty of Medicine, Chiang Mai University granted an exempt research determination to this study protocol (No. EXEMPTION-7046/2020).

Availability of data and material

All data used to support the findings of this study are available from the corresponding author upon reasonable request.

Authors’ contributions

NK and MN contributed to the study conception and design; WS and MN conducted the study and extracted the data under supervision of NK; all authors analyzed the data and interpreted the results; and NK wrote the manuscript, with contributions from all authors.

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Na Takuathung, M., Sakuludomkan, W. & Koonrungsesomboon, N. The Impact of Genetic Polymorphisms on the Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid: Systematic Review and Meta-analysis. Clin Pharmacokinet 60, 1291–1302 (2021). https://doi.org/10.1007/s40262-021-01037-7

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  • DOI: https://doi.org/10.1007/s40262-021-01037-7

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