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

作者：Pouche Lucie; Koitka Matthias; Stojanova Jana; Woillard Jean Baptiste; Monchaud Caroline; Villeneuve Claire; Essig Marie; Abraham Julie; Le Meur Yannick; Rerolle Jean Phillippe; Kamar Nassim; Rostaing Lionel; Merville Pierre; Gandia Peggy; Bouchet Stephane; Petersen Britt Sabina; Marquet Pierre; Picard Nicolas^*

来源：Pharmacogenomics, 2016, 17(4): 375-391.

DOI：10.2217/pgs.15.181

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

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.

• 出版日期2016-3