Effect of Genetic Polymorphism on Calcineurin Inhibitors Levels in Egyptian Renal Transplant Patients

Renal transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Calcineurin Inhibitors tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection. The aim of the present study is to detect the incidence of some selected genetic polymorphism in Egyptian renal transplant population and investigate the influence of these genetic polymorphism (SNPs )on Cyclosporine and Tacrolimus blood concentration. In addition to detect the association between these genetic polymorphism variants and patients' clinical outcome after transplantation.

Tacrolimus and cyclosporine are the principle immunosuppressive agents administered to solid organ transplant recipients to prevent and treat allograft rejection.They both exert their immunosppressive action by inhibiting the calcinurein in T-lymphoctes. Subsequently,Cyclosporin and tacrolimus are both metabolic substrates for cytochrome P450 (CYP) 3A enzymes - in particular, CYP3A4 and CYP3A5 - and are transported out of cells by the P-glycoprotein (ABCB1) efflux pump. Different expression of CYP3A4, CYP3A5 and P-glycoprotein causes patient to-patient variability in the absorption, metabolism and tissue distribution of calcineurin inhibitors. This different expression is likely to be at least partially the result of mutations in the genes encoding for these enzymes and drug transporter. This may lead to variable drug concentrations within the systemic circulation and at target sites, influencing drug efficacy. Moreover, it will influence the individual's susceptibility to drug interactions and drug toxicity