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CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine

The Pharmacogenomics Journal volume 8, pages 416–422 (2008)Cite this article

Abstract

The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6±3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29–0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.

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Acknowledgements

This study was supported by a grant from Novartis Transplantation and Immunology to JB and RK.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    R Kreutz, J Bolbrinker & S Kain

  2. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

    F van der Sman-de Beer & F W Dekker

  3. Hans Mak Institute, Naarden, The Netherlands

    E W Boeschoten

  4. Department of Medical Informatics, Biometry and Epidemiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    P Martus

  5. Leibniz-Institut für Arterioskleroseforschung, Münster, Leipzig, Germany

    A Sietmann, F Friedrichs & M Stoll

  6. Department of Medicine Nephrology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

    G Offermann

  7. Department of Medicine Nephrology, Klinikum St Georg, Leipzig, Germany

    J Beige

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  1. R Kreutz
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  2. J Bolbrinker
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  3. F van der Sman-de Beer
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  6. S Kain
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  7. P Martus
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  11. G Offermann
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  12. J Beige
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Correspondence to R Kreutz.

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The authors declare that they have no competing financial interests.

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Kreutz, R., Bolbrinker, J., van der Sman-de Beer, F. et al. CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine. Pharmacogenomics J 8, 416–422 (2008). https://doi.org/10.1038/sj.tpj.6500488

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  • DOI: https://doi.org/10.1038/sj.tpj.6500488

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