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

Abstract Background Liver 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. Aim of the Work To assess the influence of CYP3A5 rs776746 gene polymorphism on tacrolimus dose and its role in individualizing tacrolimus dose in Egyptian liver transplant recipient. Patients and Methods The study included 25 liver transplant recipients and their corresponding donors. CYP3A5 gene polymorphism was done to all participants by RTPCR. For recipients, tacrolimus trough level was measured and tacrolimus weight adjusted dose was recorded. Drug concentration over dose ratio was calculated (C/D ratio). Results The present study showed that recipients carrying 3*1 and 1*1 genotypes required higher dose of tacrolimus than recipients with 3*3 genotype but was not statistical significance. Donors carrying 3*1 and 1*1 genotypes, their corresponding recepients needed higher doses of tacrolimus to achieve the desired trough levels and thus lower C/D ratio compared to recipients with donors carrying 3*3 genotype with statistically significant difference in the first month post transpalnt. Conclusion The present study revealed that recipients and grafts carrying 3*1 and 1*1 genotypes require higher dose of tacrolimus than those with 3*3 genotype. Effect of graft’s CYP3A5 genotype has higher significance than recipient’s genotype on tacrolimus dose and C/D ratio.