CYP3A5*3 Genetic Polymorphism and Tacrolimus Concentration in Myanmar Renal Transplant Patients

Abstract

BackgroundGenetic polymorphism is an important factor that influences tacrolimus concentrations and has the potential to predict the optimal dosage of tacrolimus in personalized medicine. Tacrolimus, a drug of narrow therapeutic index, is used in renal transplant recipients as an immunosuppressant agent. It is a substrate of cytochrome P450 3A (CYP3A) and has highly variable pharmacokinetic parameters. ObjectiveThe aim of this study was to identify the proportion of CYP3A5 gene polymorphism in Myanmar kidney transplant recipients and to determine the impact of CYP3A5 gene polymorphisms on tacrolimus level in CYP3A5 expressors and nonexpressors. MethodsThis study included 41 adult Myanmar post–renal transplant patients. Tacrolimus trough blood levels were determined and CYP3A5 genotype analysis was conducted by using polymerase chain reaction amplification of target followed by detection by restriction fragment length polymorphism analysis.Results. The CYP3A5 nonexpressors and expressors were detected in 25 (60.97%) and 16 (39.02%) of the 41 renal transplant recipients, respectively. The tacrolimus concentration/dose ratio in the CYP3A5 expressor group was lower than in the CYP3A5 nonexpressor group (1.49 ± 0.69 vs 3.49 ± 3.08 [P = .003] at 1 month; and 1.54 ± 0.9 vs 7.88 ± 8.25 [P = .0001] at 3 months). ConclusionsThe findings of the present study revealed that more than one half of the study population were carrying the mutant allele CYP3A5*3(A6986G). CYP3A5 genetic polymorphism is one of the important factors in determining daily requirements for tacrolimus and in adjusting tacrolimus trough concentrations.