The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients.

The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C0/D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients. Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C0/D at 5, 10, 15, and 30 days after transplantation. Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C0/D than those with the TC/CC genotype (p   T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p   T and CYP3A5 6986A > G influence the TAC C0/D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period.