Study of the Effect of CYP3A5 Single Nucleotide Polymorphism on Tacrolimus Metabolism in Liver Transplant Patients

Abstract

iver transplantation (LT) is currently recognized as the most effective treatment for all types of end stage liver diseases. Major advances have been made in the field of liver transplantation due to improvements in surgical techniques and organ conservation as well as optimization of intensive care and immunosuppressive management. Immunosuppressant is mandatory for the prevention and treatment of graft rejection. The appropriate choice and use of immunosuppressant is directly related to the survival of liver transplant recipients. Immunosuppressive agents are required in liver transplantation for induction of immunosuppression in the early phase, maintenance of immunosuppression in the late phase or for the treatment of graft rejection. FK506 (tacrolimus) is a powerful and selective anti-T-lymphocyte agent, with a mechanism of action similar to that of cyclosporine, it binds to an intracellular receptor and subsequently binds to calcineurin and inhibits the calcineurin pathway that stimulate the transcription factor Nuclear factor of activated T cells (NFAT). Dephosphorylated NF-AT translocate to the nucleus, where it binds to specific DNA sites in the promoter regions of several cytokine genes, including interleukin (IL)-2. Through this series of actions, tacrolimus inhibit transcription of IL-2 thus inhibit proliferation and differentiation of T cells producing immunosuppression.