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Pharmacogenomics. 2016 Mar;17(4):375-91. doi: 10.2217/pgs.15.181. Epub 2016 Feb 19.

A candidate gene approach of the calcineurin pathway to identify variants associated with clinical outcomes in renal transplantation.

Author information

1
Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
2
Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.
3
CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
4
Laboratory of Chemical Carcinogenesis & Pharmacogenetics, University of Chile, Santiago, Chile.
5
CHU Limoges, Department of Nephrology, Dialysis & Transplantation, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
6
CHU Limoges, Department of Clinical Hematology, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
7
CHU Brest, Hôpital Cavale Blanche, Department of Nephrology, F-29609 Brest, France.
8
CHU Toulouse Rangueil, Department of Nephrology & Organ Transplantation, F-31000 Toulouse, France.
9
INSERM, U1043, Structure Fédérative de Recherche Bio-Médicale de Toulouse (SFR-BMT), Centre Hospitalier Universitaire (CHU) Purpan, Toulouse, France.
10
Université Paul Sabatier, 118 route de Narbonne, F-31062 Toulouse, France.
11
CHU Bordeaux, Department of Nephrology, Transplantation, Dialysis, F-33000 Bordeaux, France.
12
CHU Toulouse, Laboratory of Pharmacokinetics & Clinical Toxicology, F-31000 Toulouse, France.
13
CHU Bordeaux, Department of Clinical Pharmacology & Toxicology, F-33000 Bordeaux, France.
14
Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Germany.

Abstract

AIM:

To investigate the potential influence of variants in genes involved in the calcineurin pathway on the efficacy and toxicity of calcineurin inhibitors in renal transplantation.

MATERIALS & METHODS:

Twenty-three polymorphisms in thirteen genes were tested in 381 renal transplant recipients receiving ciclosporin (n = 221) or tacrolimus (n = 160) and mycophenolate mofetil. Data were collected prospectively over the first year post-transplantation.

RESULTS:

Multivariate survival analyses revealed no genetic associations with biopsy proven acute graft rejection and serious infections. Donor-recipient Cytomegalovirus mismatch was the only variable associated with serious infection.

CONCLUSION:

This large exploratory study casts doubts on the potential interest of genetic biomarkers related to CNI pharmacodynamics but associations with other phenotypes in transplantation deserve further studies.

KEYWORDS:

acute rejection; calcineurin; ciclosporin; genetic polymorphism; kidney transplantation; opportunistic infections; pharmacogenetics; tacrolimus

PMID:
26894651
DOI:
10.2217/pgs.15.181
[Indexed for MEDLINE]

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