The Effect of ABCB1 Polymorphisms on Serial Tacrolimus Concentrations in Stable Austrian Long-Term Kidney Transplant Recipients.

Abstract

The multidrug resistance 1 gene (ABCB1) encodes P-glycoprotein (PGP), mainly expressed in the liver and engaged in metabolism of drugs including the immunosuppressant tacrolimus (TAC). ABCB1 single nucleotide polymorphisms (SNP) may significantly alter pharmacokinetics and influence TAC concentrations of kidney transplant recipients (KTR). The genotype distribution of ABCB1 1236C>T, 2677G>T/A and 3435C>T was investigated among 96 Austrian KTR who were converted from cyclosporin to TAC. Dose adjusted TAC trough levels and L/D ratios were assessed at week 1, 2, 4, and 8, and month 3, 12, and 24, and the influence of ABCB1 genotypes on dose adjusted TAC trough levels and level to dose (L/D) ratios were analyzed. The genotype distributions for ABCB1 1236C>T were CC 36.4%, CT 5.2%, TT 58.3%, for ABCB1 2677G>T/A GA 2%, GG 63.5%, GT 20.8%, TA 1%, TT 12.5%, and for ABCB1 3435C>T CC 20.8%, CT 7.2%, TT 71.8%. Dose adjusted TAC trough levels and L/D ratios were independent of ABCB1 genotypes except for ABCB1 1236C>T at a single time point (week 2: 0.02599 [CC] vs. 0.05704 [CT] vs. 0.03218 [TT]; p = 0.024). Serial analyses of TAC trough levels revealed no significant association with important ABCB1 genotypes among stable long-term Austrian KTR.