title: A candidate gene approach of the calcineurin pathway to identify variants associated with clinical outcomes in renal transplantation.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Pouché
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.
authors.forename: Matthias
authors.initials: M
authors.lastname: Koitka
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|Laboratory of Chemical Carcinogenesis & Pharmacogenetics, University of Chile, Santiago, Chile.
authors.forename: Jana
authors.initials: J
authors.lastname: Stojanova
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Woillard
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Monchaud
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Villeneuve
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|CHU Limoges, Department of Nephrology, Dialysis & Transplantation, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Essig
authors.affiliation: CHU Limoges, Department of Clinical Hematology, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Abraham
authors.affiliation: CHU Brest, Hôpital Cavale Blanche, Department of Nephrology, F-29609 Brest, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Meur
authors.affiliation: CHU Limoges, Department of Nephrology, Dialysis & Transplantation, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Jean-Phillippe
authors.initials: JP
authors.lastname: Rerolle
authors.affiliation: CHU Toulouse Rangueil, Department of Nephrology & Organ Transplantation, F-31000 Toulouse, France.|INSERM, U1043, Structure Fédérative de Recherche Bio-Médicale de Toulouse (SFR-BMT), Centre Hospitalier Universitaire (CHU) Purpan, Toulouse, France.|Université Paul Sabatier, 118 route de Narbonne, F-31062 Toulouse, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.affiliation: CHU Toulouse Rangueil, Department of Nephrology & Organ Transplantation, F-31000 Toulouse, France.|INSERM, U1043, Structure Fédérative de Recherche Bio-Médicale de Toulouse (SFR-BMT), Centre Hospitalier Universitaire (CHU) Purpan, Toulouse, France.|Université Paul Sabatier, 118 route de Narbonne, F-31062 Toulouse, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
authors.affiliation: CHU Bordeaux, Department of Nephrology, Transplantation, Dialysis, F-33000 Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.affiliation: CHU Toulouse, Laboratory of Pharmacokinetics & Clinical Toxicology, F-31000 Toulouse, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Gandia
authors.affiliation: CHU Bordeaux, Department of Clinical Pharmacology & Toxicology, F-33000 Bordeaux, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Bouchet
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Germany.
authors.forename: Britt-Sabina
authors.initials: BS
authors.lastname: Petersen
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
mesh_terms: D000328:Adult; D019703:Calcineurin / Q000378:metabolism*; D016572:Cyclosporine / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006084:Graft Rejection / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016720:Pneumocystis Infections / Q000235:genetics / Q000382:microbiology; D045363:Pneumocystis carinii; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D015398:Signal Transduction; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: acute rejection; calcineurin; ciclosporin; genetic polymorphism; kidney transplantation; opportunistic infections; pharmacogenetics; tacrolimus