Effect of CYP3A5 gene polymorphisms on tacrolimus concentration in pediatric liver transplant patients

Objective To evaluate the effect of cytochrome P450(CYP)3A5 genes of both donors and recipients on the concentration/dosage ratio(C/D) of tacrolimus in pediatric liver transplant patients. Methods A total of 127 pediatric liver transplant patients received tacrolimus. CYP3A5 polymorphism of donors and recipients were measured at the time of transplantation and then tacrolimus-based immunosuppressive therapy was started on the basis of individual genetic constitution. CYP3A5*1/*1 genotype and *1/*3 genotype were combined into expressor genotype and *3/*3 genotype non-expressor group. The C/D of tacrolimus during 3 months after surgery was analyzed in relation to CYP3A5 genotype. Results C/D of tacrolimus in patients with CYP3A5*1 expressed donor was lower than C/D of patients with CYP3A5*1 unexpressed donor (P 0.05). Conclusions CYP3A5*1 genotype in donors as well as in patients both contributes to inter-individual variation in C/D of tacrolimus during adult liver transplantation. The recipients with CYP3A5* 1 allelic genes need a higher optimal dose of tacrolimus. Patients can benefit from setting and adjusting FK506 doses according to CYP3A5 genotype of both donors and recipients. Key words: Liver transplantation; Tacrolimus blinding proteins; Genotype