23 March 2011
Polymorphisms in CYP3A5*3 and MDR1, and haplotype modulate response to plasma levels of Tacrolimus in Chinese renal transplant patientsPing WuACDEF, Xuefeng NiACDEF, Mingli WangADG, Xianlin XuABD, Guanghua LuoDF, Yan JiangB
Ann Transplant 2011; 16(1): 54-60 :: ID: 881639
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
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