Association of SNPs with the efficacy and safety of immunosuppressant therapy after heart transplantation

Pharmacogenomics. 2015;16(9):971-9. doi: 10.2217/pgs.15.39. Epub 2015 Jun 24.

Abstract

Aim: Studying the possible influence of SNPs on efficacy and safety of calcineurin inhibitors upon heart transplantation.

Materials & methods: In 60 heart transplant patients treated with tacrolimus or cyclosporine, we studied a panel of 36 SNPs correlated with a series of clinical parameters during the first post-transplantation year.

Results: The presence of serious infections was correlated to ABCB1 rs1128503 (p = 0.012), CC genotype reduced the probability of infections being also associated with lower blood cyclosporine concentrations. Lower renal function levels were found in patients with rs9282564 AG (p = 0.003), related to higher blood cyclosporine blood levels. A tendency toward increased graft rejection (p = 0.05) was correlated to rs2066844 CC in NOD2/CARD15, a gene related to lymphocyte activation.

Conclusion: Pharmacogenetics can help identify patients at increased risk of clinical complications. Original submitted 30 January 2015; revision submitted 27 March 2015.

Keywords: cyclosporine; graft rejection; infection; polymorphism; renal function; tacrolimus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Aged
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacokinetics
  • Cyclosporine / therapeutic use
  • Female
  • Graft Rejection / genetics*
  • Graft Rejection / prevention & control*
  • Heart Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Infections / epidemiology
  • Kidney / metabolism
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Tacrolimus / adverse effects
  • Tacrolimus / pharmacokinetics
  • Tacrolimus / therapeutic use
  • Tissue Donors

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Immunosuppressive Agents
  • Cyclosporine
  • Tacrolimus