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

Author:

Pouché Lucie123,Koitka Matthias12,Stojanova Jana124,Woillard Jean-Baptiste123,Monchaud Caroline13,Villeneuve Claire123,Essig Marie125,Abraham Julie6,Le Meur Yannick7,Rerolle Jean-Phillippe5,Kamar Nassim8910,Rostaing Lionel8910,Merville Pierre11,Gandia Peggy12,Bouchet Stephane13,Petersen Britt-Sabina14,Marquet Pierre123,Picard Nicolas123

Affiliation:

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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