1. A candidate gene approach of the calcineurin pathway to identify variants associated with clinical outcomes in renal transplantation
- Author
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Jana Stojanova, Nicolas Picard, Jean-Baptiste Woillard, Peggy Gandia, Pierre Marquet, Yannick Le Meur, Marie Essig, Pierre Merville, Lionel Rostaing, Claire Villeneuve, Stéphane Bouchet, Lucie Pouché, Britt-Sabina Petersen, Jean-Phillippe Rerolle, Nassim Kamar, Matthias Koitka, Julie Abraham, and Caroline Monchaud
- Subjects
Adult ,Graft Rejection ,Male ,Risk ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Candidate gene ,Biology ,Pneumocystis carinii ,Polymorphism, Single Nucleotide ,Tacrolimus ,Mycophenolic acid ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genetics ,medicine ,Humans ,Prospective Studies ,Genetic Association Studies ,Kidney transplantation ,Pharmacology ,Calcineurin ,Middle Aged ,Mycophenolic Acid ,Ciclosporin ,medicine.disease ,Kidney Transplantation ,Pneumocystis Infections ,Transplantation ,surgical procedures, operative ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cytomegalovirus Infections ,Immunology ,Cyclosporine ,Molecular Medicine ,Female ,Immunosuppressive Agents ,Pharmacogenetics ,Signal Transduction ,medicine.drug - 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.
- Published
- 2016
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