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Regenerative Medicine

Attempted validation of 44 reported SNPs associated with tacrolimus troughs in a cohort of kidney allograft recipients

    William S Oetting

    *Author for correspondence: Tel.: +1 612 624 1139; Fax: +1 612 624 6645;

    E-mail Address: oetti001@umn.edu

    Department of Experimental & Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA

    ,
    Baolin Wu

    Department of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA

    ,
    David P Schladt

    Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA

    ,
    Weihua Guan

    Department of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA

    ,
    Rory P Remmel

    Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA

    ,
    Casey Dorr

    Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA

    Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA 

    ,
    Roslyn B Mannon

    Division of Nephrology, University of Alabama, Birmingham, AL 35233, USA

    ,
    Arthur J Matas

    Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA

    ,
    Ajay K Israni

    Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA

    Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA

    Department of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN 55455, USA

    &
    Pamala A Jacobson

    Department of Experimental & Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA

    Published Online:https://doi.org/10.2217/pgs-2017-0187

    Aim: Multiple genetic variants have been associated with variation in tacrolimus (TAC) trough concentrations. Unfortunately, additional studies do not confirm these associations, leading one to question if a reported association is accurate and reliable. We attempted to validate 44 published variants associated with TAC trough concentrations. Materials & methods: Genotypes of the variants in our cohort of 1923 kidney allograft recipients were associated with TAC trough concentrations. Results: Only variants in CYP3A4 and CYP3A5 were significantly associated with variation in TAC trough concentrations in our validation. Conclusion: There is no evidence that common variants outside the CYP3A4 and CYP3A5 loci are associated with variation in TAC trough concentrations. In the future rare variants may be important and identified using DNA sequencing.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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