Polymorphisms in CYP3A5*3 and MDR1, and haplotype modulate response to plasma levels of Tacrolimus in Chinese renal transplant patients
Ping Wu, Xuefeng Ni, Mingli Wang, Xianlin Xu, Guanghua Luo, Yan Jiang
Ann Transplant 2011; 16(1): 54-60
Available online: 2011-03-23
Background: The purpose of this study was to investigate the effects of polymorphisms in CYP3A5*3, CYP3AP1, and MDR1, and of haplotype, on plasma levels of tacrolimus in Chinese patients after renal transplantation, and to assess the relationship between polymorphisms and the variability of concentration/dose of tacrolimus for optimization and individualization regimens.
Material/Methods: The MALDI-TOF method was used to detect the genotype of CYP3A5*3, CYP3AP1, and MDR-1 in kidney transplant recipients (n=63) receiving tacrolimus. Patients were assigned to 3 groups according to genotype. Peripheral blood was collected and the serum concentrations of tacrolimus were determined by EMIT 2000 after 12 hours of administration. Dose-adjusted concentrations of tacrolimus were calculated according to the different groups.
Results: We found that tacrolimus dose-adjusted C0 was larger in CYP3A5*3 and CYP3AP1 non-expressing renal transplant patients than in those who expressed the genes. In addition, wild-type homozygotes for MDR1 C3435T had a slightly lower dose-adjusted C0 compared with heterozygotes. However, no evidence was found that there was relationship between the MDR1 1236CT, 2677GT or haplotype polymorphisms and tacrolimus pharmacokinetics.
Conclusions: The CYP3A5 genotype shows the most important association with tacrolimus concentrations. Our study suggests that a pharmacogenetic approach could be employed to predict individual drug availability differences in future.
Keywords: Tacrolimus, renal transplantation, Polymorphism, MDR1, CYP3AP1, CYP3A5