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Effect of CYP3A5 and MDR1 Gene Polymorphism in both Donor and Recipient on Concentration/Dose Ratios of Tacrolimus in Liver Transplant Patients

LI Yang,JIANG Nan,GUO Yu,CHEN Guan-zhong,ZHANG Qi,LU Min-qiang,YANG Yang,CHEN GUI-hua(Department of Liver Surgery and Liver Transplantation Center,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China)  
【Objective】 To investigate the effect of CYP3A5 and MDR1 polymorphism in the donor/recipient on the concentration /dose ratio of Tacrolimus in Chinese liver transplant patients.【Methods】 Blood samples were collected from liver transplant patients who received Tacrolimus in the third affiliated hospital of Sun Yat-sen university,and the tissue samples were collected from the corresponding donors.The CYP3A5 andMDR1 genotypes were determined by PCR-RFLP method.At 1,2,4 and 12 weeks after transplantation,Tacrolimus doses(mg/kg/day) and trough blood levels(C0) were determined.【Results】 The concentration /dose ratios of patients with CYP3A51 /1 and CYP3A5 1/3 donors were significantly lower than those with CYP3A53/3 patients at 2,4 and 12 weeks after liver transplantation.No difference was found among the MDR1 genotypes in donor /recipients or CYP3A5 genotypes in recipients.The same results were found in the analysis of the combination of both dornors and recipients.【Conclusion】 CYP3A5 1/ 3 polymorphism in the donor is correlated with the whole blood concentration /dose ratio in Chinese liver transplant patients.Donors with CYP3A5 1 allele require more tacrolimus to reach target concentrations compared to those with CYP3A5 3/ 3 genotype.
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