ABCMdb

PMID: 19545654

Rosso Felipe C, de Sandes TV, Sampaio EL, Park SI, Silva HT Jr, Medina Pestana JO
Clinical impact of polymorphisms of transport proteins and enzymes involved in the metabolism of immunosuppressive drugs.
Transplant Proc. 2009 Jun;41(5):1441-55., [PubMed]

Sentences

No. Mutations Sentence Comment

116 ABCC4 p.Glu757Lys ABCC4 p.Thr1142Met ABCC4 p.Tyr556Cys This mutation is relatively common (Ͼ18%) in the Japanese population and is associated with increased sensitivity to thiopurines observed in some Japanese patients.72 In one study, 4 MRP4 missense genetic variants (Y556C, E757K, V7761, and T1142M) exhibited a 20% to 40% reduced expression level compared with the wild type. Login to comment 198 ABCC2 p.Gly699Ala In one study including 87 Japanese kidney transplant recipients, carriers of the SNP (T334G or G699A) of one OATP transport member (SLCO1 B3), which have increased uptake transport activity, showed higher dose-adjusted MPA exposure compared with wild-type carriers. Login to comment 206 ABCB1 p.Gly1249Ala ABCB1 p.Gly1249Ala Influence of Genetic Polymorphisms of Drug Transporters and Metabolizing Enzymes on Mycophenolic Acid Pharmacokinetics Population Investigated Polymorphisms Findings References 95 de novo kidney transplant recipients receiving MMF/TAC/ steroids UGT1A9 C-2152T, T-275A - 86 MRP2C-24T, C3972T (CC, CT, TT) Lower MPA AUC0-12* MRP2 G-1549A, G-1023A, A-1019G, G1249A - 95 de novo kidney transplant recipients receiving MMF/TAC/ steroids UGT1A9 T-275A, C-2152T Lower MPA C0 and AUC0-12 95 40 renal transplant recipients receiving MMF/CSA UGT1A9 C-440T, T-331C Lower/higher MPA AUC0-12 96 (Caucasian) ABCC2-C-24T, G1249A - 80 renal transplant recipients receiving MMF/TAC UGT1A7 (*1/*1, *1/*2, *1/*3, *2/*3, *3/*3) No difference in MPA AUC0-12 98 (Japanese) UGT1A9 intronic 1399 (CC, CT, TT) 92 renal transplant recipients receiving MMF/SRL UGT2B7 G-842A (GG, GA, AA) Higher Acyl-MPA AUC0-9 ߤ 99 (n afd; 40), TAC/MMF (n afd; 24), CsA/ MMF, (n afd; 28) 72 renal transplant recipients receiving MMF/TAC UGT1A8 (*1/*1, *1/*2, *2/*2) No difference in MPA AUC0-12 100 (Japanese) 87 renal transplant recipients receiving MMF/TAC OATP/SLCO1B1 (*1/*1, *1/*3, *3/*3) No difference in MPA AUC0-12 103 (Japanese) ABCC2 C-24T (CC, CT, TT) No difference in MPA AUC0-12 MMF, mycophenolate mofetil; TAC, tacrolimus; CsA, cyclosporine; SRL, sirolimus; MPA, mycophenolic acid; AUC, area under the concentration-time curve; C0, trough concentrations; -, no effect. Login to comment 207 ABCB1 p.Gly1249Ala ABCB1 p.Gly1249Ala Influence of Genetic Polymorphisms of Drug Transporters and Metabolizing Enzymes on Mycophenolic Acid Pharmacokinetics Population Investigated Polymorphisms Findings References 95 de novo kidney transplant recipients receiving MMF/TAC/ steroids UGT1A9 C-2152T, T-275A - 86 MRP2C-24T, C3972T (CC, CT, TT) Lower MPA AUC0-12* MRP2 G-1549A, G-1023A, A-1019G, G1249A - 95 de novo kidney transplant recipients receiving MMF/TAC/ steroids UGT1A9 T-275A, C-2152T Lower MPA C0 and AUC0-12 95 40 renal transplant recipients receiving MMF/CSA UGT1A9 C-440T, T-331C Lower/higher MPA AUC0-12 96 (Caucasian) ABCC2-C-24T, G1249A - 80 renal transplant recipients receiving MMF/TAC UGT1A7 (*1/*1, *1/*2, *1/*3, *2/*3, *3/*3) No difference in MPA AUC0-12 98 (Japanese) UGT1A9 intronic 1399 (CC, CT, TT) 92 renal transplant recipients receiving MMF/SRL UGT2B7 G-842A (GG, GA, AA) Higher Acyl-MPA AUC0-9 † 99 (n ϭ 40), TAC/MMF (n ϭ 24), CsA/ MMF, (n ϭ 28) 72 renal transplant recipients receiving MMF/TAC UGT1A8 (*1/*1, *1/*2, *2/*2) No difference in MPA AUC0-12 100 (Japanese) 87 renal transplant recipients receiving MMF/TAC OATP/SLCO1B1 (*1/*1, *1/*3, *3/*3) No difference in MPA AUC0-12 103 (Japanese) ABCC2 C-24T (CC, CT, TT) No difference in MPA AUC0-12 MMF, mycophenolate mofetil; TAC, tacrolimus; CsA, cyclosporine; SRL, sirolimus; MPA, mycophenolic acid; AUC, area under the concentration-time curve; C0, trough concentrations; -, no effect. Login to comment