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

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

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Calcineurin / metabolism*
  • Cyclosporine / therapeutic use
  • Cytomegalovirus Infections / genetics
  • Female
  • Genetic Association Studies
  • Graft Rejection / genetics
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Pneumocystis Infections / genetics
  • Pneumocystis Infections / microbiology
  • Pneumocystis carinii
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Risk
  • Signal Transduction
  • Tacrolimus / therapeutic use

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Calcineurin
  • Mycophenolic Acid
  • Tacrolimus