Effect of CYP 3A4*1B and CYP3A5*3 Gene Polymorphisms in Antirejection of Tacrolimus in Liver Transplant Patients.

Abstract

Background: Tacrolimus is a substrate of CYP 3A5; to reduce the rate of liver injury and rejection in liver transplant (LT) recipients, it is feasible to optimize the administration of tacrolimus by adding CYP gene polymorphism.

Methods: We divided 151 LT recipients randomly into an optimization group and a control group. All were tested routinely for clinical indicators such as FK506 trough concentration and biochemistry, and their complications and survival were observed. The optimization group additionally detected single nucleotide polymorphisms in the CYP 3A4*1B and CYP 3A5*3 genes.

Results: There were no significant differences in tacrolimus dosage, FK506 trough concentrations, and concentration/dose value between the 2 groups. In the optimization group, all patients tested CYP 3A4*1B as wild type. CYP 3A5*3 detection classification included 35 with the G/G mutation (45.5%) and 36 A/G wild-type individuals (46.8%). The concentration/dose values of G/G mutant patients were significantly higher than those of A/G wild-type and A/A mutant patients (G/G vs. A/G; P < .05), and no significant difference in FK506.

Conclusion: The CYP 3A4*1B genotype has less influence on tacrolimus metabolism. The genetic polymorphism of CYP 3A5*3 is obvious and largely affects tacrolimus metabolism, and the variant patients need lower doses of tacrolimus to reach the target concentration.