Cyp3a5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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  Download references ACKNOWLEDGEMENTS This study was supported by a grant from Novartis Transplantation and Immunology to JB and RK. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department

of Clinical Pharmacology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany R Kreutz, J Bolbrinker & S Kain * Department of Clinical Epidemiology, Leiden

University Medical Center, Leiden, The Netherlands F van der Sman-de Beer & F W Dekker * Hans Mak Institute, Naarden, The Netherlands E W Boeschoten * Department of Medical Informatics,

Biometry and Epidemiology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany P Martus * Leibniz-Institut für Arterioskleroseforschung, Münster, Leipzig, Germany A

Sietmann, F Friedrichs & M Stoll * Department of Medicine Nephrology, Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany G Offermann * Department of Medicine

Nephrology, Klinikum St Georg, Leipzig, Germany J Beige Authors * R Kreutz View author publications You can also search for this author inPubMed Google Scholar * J Bolbrinker View author

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Duality of Interest The authors declare that they have no competing financial interests. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 18 July 2007 * Revised: 02 November 2007 * Accepted: 26 November 2007 *

Published: 08 January 2008 * Issue Date: December 2008 * DOI: https://doi.org/10.1038/sj.tpj.6500488 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * transplantation * kidney * cyclosporine * CYP3A5