Effect of Genetic Polymorphism on Clinical Efficacy of Tacrolimus in Adult Living Donor-Liver Transplant Patients

Abstract

Background and Aim The influence of genetic polymorphism on the clinical outcome including response and safety of immunosuppression in liver transplant (LT) recipients remains controversial among different races and ethnicities, especially for calcineurin inhibitors (CNIs). This study aims to evaluate the effect of different genotypes of the single nucleotide polymorphism (SNP) in the genes encoding CYP3A5 on the therapeutic response to the widely used calcineurin inhibitor; tacrolimus. Method In 49 living donor liver transplant (LDLT) recipients with tacrolimus as the backbone immunosuppressive, the rejection, delayed graft function, laboratory evidenced nephrotoxicity, new onset diabetes and hypertension rates were considered the primary therapeutic and safety outcomes of tacrolimus. The biochemical parameters of tacrolimus response and safety as evidence by the status of liver functions, renal functions, complete blood counts and serum electrolytes, as well as the need for Mycophenolate mofetil (MMF) were considered the secondary outcomes. Results the rejection and delayed graft function rates didn’t differ significantly among different genotypes (p = 1), similarly; the incidence of new onset diabetes and hypertension didn’t differ significantly among different genotypes (p = 1, and 0.4143 respectively). Moreover; laboratory evidenced nephrotoxicity rates didn’t differ significantly among different genotypes (p = 0.5040). No significant intergenotype differences were observed in the all biochemical outcomes. However the need for MMF was significantly higher among carriers of the CYP3A5*3 allele. Conclusion different genotypes did not offer an advantage over one another in predicting therapeutic response or toxicity of tacrolimus among LDLT recipients.