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The effect of CYP3A5 polymorphism on dose-adjusted cyclosporine concentration in renal transplant recipients: a meta-analysis

The Pharmacogenomics Journal volume 11, pages 237–246 (2011)Cite this article

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Abstract

Cyclosporine (CsA) is a substrate of cytochrome P450 (CYP) 3A5 and has a narrow therapeutic range with large inter-individual variability. CYP3A5*3 polymorphism is reported to be functional and may contribute to the inter-individual variability. The objective of this meta-analysis was to accurately estimate the effect of CYP3A5*3 allele on CsA dose-adjusted blood concentration. A computerized literature search was conducted in PubMed. A total of 12 and 6 studies meeting the inclusion criteria were, respectively, included in meta-analysis about dose-adjusted trough concentration (C0/D) and dose-adjusted peak concentration (C2/D). The combined weighted mean difference (WMD) between CYP3A5 expressers (*1/*3 + *1/*1) and non-expressers (*3/*3) was significant in C2/D (WMD=−12.73 (ng ml–1)/(mg kg–1), 95% confidence interval (CI) −25.23 to −0.22, P=0.046), whereas it was marginally significant in C0/D (WMD=−3.75 (ng ml–1)/(mg kg–1), 95% CI −7.58 to 0.07, P=0.054). Exclusion of an outlier study greatly increased the association of CYP3A5 polymorphism with C0/D to be significant (WMD=−4.92 (ng ml–1)/(mg kg–1), 95% CI: −8.27 to −1.58, P=0.011). This meta-analysis showed that CYP3A5*3 polymorphism is associated with CsA dose-adjusted concentration in renal transplant recipients. Patients carrying the CYP3A5*3/*3 genotype will require a lower dose of CsA to reach target levels compared with the CYP3A5*1/*1 or *1/*3 carriers.

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Acknowledgements

This work was supported by the Nanjing Health Bureau Foundation (Grant. no. ZKX08029).

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Authors and Affiliations

  1. Division of Clinical Pharmacy, Department of Pharmacy, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China

    H J Zhu, S H Yuan, Y Fang & W H Ge

  2. Department of Urology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China

    X Z Sun

  3. Department of Respiratory Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    H Kong

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  1. H J Zhu
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Correspondence to W H Ge.

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Zhu, H., Yuan, S., Fang, Y. et al. The effect of CYP3A5 polymorphism on dose-adjusted cyclosporine concentration in renal transplant recipients: a meta-analysis. Pharmacogenomics J 11, 237–246 (2011). https://doi.org/10.1038/tpj.2010.26

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