title: ATP-binding cassette transporters as pharmacogenetic biomarkers for kidney transplantation.
abstract: Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute rejection. However, the clinical use of these drugs is complicated by the fact that they display highly variable pharmacokinetics and pharmacodynamics between individual patients. The influence of genetic variation on the interindividual variability in immunosuppressive drug disposition, efficacy, and toxicity has been explored in recent years. The polymorphically-expressed ATP-binding cassette (ABC) transporter proteins, in particular ABCB1 and ABCC2, have been investigated extensively because they play an important role in the absorption, distribution and elimination of many immunosuppressive drugs in use today. From these studies it can be concluded that polymorphisms in ABCB1 and ABCC2 have no consistent effect on immunosuppressant pharmacokinetics and toxicity although polymorphisms in ABCB1 appear to be related to the risk of developing calcineurin inhibitor-related nephrotoxicity. However, the latter needs to be replicated before an individual's ABCB1 genotype can become a useful marker that is applied in clinical practice. Future studies evaluating the influence of ABC transporter gene polymorphisms should explore the relationship with intracellular rather than systemic drug concentrations further in well-designed clinical studies. Until then, single-nucleotide polymorphisms in ABC transporter genes are not suitable to act as biomarkers for solid organ transplantation.
authors: Department of Hospital Pharmacy, Clinical Pharmacology Unit, The Netherlands.
authors: Nauras
authors: N
authors: Shuker
authors: Rachida
authors: R
authors: Bouamar
authors: Willem
authors: W
authors: Weimar
authors: Ron H N
authors: RH
authors: van Schaik
authors: Teun
authors: T
authors: van Gelder
authors: Dennis A
authors: DA
authors: Hesselink
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D054316:Biomarkers, Pharmacological / Q000032:analysis*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D000089762:Multidrug Resistance-Associated Protein 2; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; D000089762:Multidrug Resistance-Associated Protein 2