Instruction effect of of CYP3A5 gene polymorphism on tacrolimus dosage after liver transplantation

Objective To evaluate the instruction effect of CYP3A5 gene polymorphisms on tacrolimus dosage adjusted trough blood concentration during the early period after liver transplantation in patients.Methods 67 liver transplantation recipients were genotyped by DNA sequencing for CYP3A5.Tacrolimus whole blood levels were measured by enzyme-linked immunospecific assay.Dose-adjusted trough blood concentrations(C) were determined and compared among different genotype groups.Results The CYP3A5*1/*1 was observed in 15 subjects(22.4%),23(34.3%) carried *1/*3,and 29(43.3%) carried *3/*3.CYP3A5*3/*3 variant was associated with significant higher tacrolimus dose at 1 week,2 week and 1 month after transplantation.The tacrolimus C/D ratios were obviously higher in recipients carrying CYP3A5*3/*3.Conclusions Genetic polymorphisms in CYP3A5 may be responsible,in part,for the large interindividual variability of tacrolimus pharmacokinetics during the early period after liver transplantation in patients.Patients in CYP3A5 non-expressors require a low dose of tacrolimus to reach target levels compared with expressors,comparing with patients carrying CYP3A5*1/1、CYP3A5*3/3.