Effects of CYP3A5 genetic polymorphisms on metabolism of tacrolimus in patients after kidney transplantation

Mingrui WANG

ABSTRACT

Objective:

To investigate the effects of different CYP3A5 genotypes on the concentrations of tacrolimus in blood of the patients after kidney transplantation, and to provide the valuable evidence for personalized administration in the patients after kidney transplantation.

Methods:

The clinical materials of 115 patients after kidney transplantation were analyzed retrospectively. The patients were divided into three groups according to the CYP3A5 genotypes CYP3A5 ∗ 1/ ∗ 1 group (11 cases), CYP3A5 ∗ 1/ ∗ 3 group (46 cases) and CYP3A5 ∗ 3/ ∗ 3 group (58 cases). The concentration/dosage (C0/D) values of tacrolimus in blood of the patients in three groups at 7 d, 1 month, 3 months, 6 months, 1 year, and 2 years after operation were detected, respectively.

Results:

Thedifferences of body mass index (BMI), age composition ratios and gender composition ratios of the patients were not significant between three groups (P>0. 05). Compared with CYP3A5 ∗ 1/ ∗ 3 group, the C0/D values of tacrolimus in blood of the patients in CYP3A5 ∗ 1/ ∗ 1 group at 7 d, 3 months, 1 year and 2 years after operation were decreased (P=0. Oil, P<0.01, P=0.022, P=0.024); compared with CYP3A5 ∗ 3/∗ 3 group, the C0/D values of tacrolimus in blood of the patients in CYP3A5 ∗ 1/ ∗ 1 group and CYP3A5 ∗ 1/ ∗ 3 group at 7 d, 1 months, 3 months, 6 months, 1 year and 2 years after operation were decreased (PCYP3A5 ∗ 1/ ∗ 1 group, the C0/D value of tacrolimus in blood of the patients at 7 d after operation was significantly lower than those at 6 months, 1 year and 2 years after operation (P=0. 004, P=0. 049, P=0. 036); in CYP3A5 ∗ 1/ ∗ 3 group, the Co /D value of tacrolimus in blood of the patients at 7 d after operation was significantly lower than those at 1 month, 3 months, 6 months, 1 year and 2 years after operation (P=0. 006, Ptacrolimus in blood of the patients at 1 month after operation was significantly lower than that at 6 months after operation (P=0. 013); in CYP3A5 ∗ 3/ ∗ 3 group, the C0/D value of tacrolimus in blood of the patients at 7 d after operation was significantly lower than those at 1 month, 3 months, 6 months, 1 year and 2 years after operation (P= 0.002, P<0. 01, P<0.01, P<0. 01, P<0.01).

Conclusion:

The CYP3A5 genetic polymorphism has a significant impact on the metabolism of tacrolimus in blood of the patients after kidney transplantation, and the impact could last for two years.