CYP3A5 rather than MDR1 gene polymorphism of recipient is related to tacrolimus individual dose requirement in Chinese liver transplant patients

摘要

AIM: Tacrolimus shows considerable interindividual pharmacokinetic variability, therapeutic drug monitoring of trough blood concentration is necessary to avoid adverse effects. CYP3A5 and P-glycoprotein (P-gp, encoded by MDR1) are involved in tacrolimus’ metabolism and absorption process. This study is to investigate whether tacrolimus dosage adjustment is affected by the polymorphism in CYP3A5 and MDR1 in Chinese liver transplant patients. METHODS: Forty-nine liver transplant patients treated with tacrolimus were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 and MDR1. Tacrolimus blood tough concentration was measured by FPIA, and concentration/dose ratio(C/D) was investigated at day 7, day 14 and 1 month after liver transplantation. RESULTS: The CD ratios in recipient with CYP3A5*1/*1 (*1/*3) were significantly lower than those of CYP3A5*3/*3 patients after liver transplantation, and the C/D ratios of CYP3A5*1/*1 ,*1/*3 and *3/*3 were shown as follows: 76, 82±18, 164±51 at 7 days; 32, 76±19, 132±31 at 14 days; 36, 65±25, 122±32 at 1 month. No significant difference was found among the MDR1 G2677T/A and C3435T genotype. CONCLUSION: There was no relationship between MDR1 gene polymorphism (C3435T, G2677T/A) and tacrolimus C/D ratio in Chinese liver transplantation patients. CYP3A5 *3 polymorphism is correlated with the whole blood concentration of tacrolimus and dose requirement. The intestinal CYP3A5 plays an important role in the metabolism of orally administered tacrolimus in the first month after liver transplantation.