title: New challenges and promises in solid organ transplantation pharmacogenetics: the genetic variability of proteins involved in the pharmacodynamics of immunosuppressive drugs.
abstract: Interindividual variability in immunosuppressive drug responses might be partly explained by genetic variants in proteins involved in the immune response or associated with IS pharmacodynamics. On a general basis, the pharmacogenetics of drug target proteins is less known and understood than that of proteins involved in drug disposition pathways. The aim of this review is to facilitate research related to the pharmacodynamics of the main immunosuppressive drugs used in solid organ transplantation. We elaborated a quality of evidence grading system based on a literature review and identified 'highly recommended', 'recommended' or 'potential' candidates for further research. It is likely that a number of additional rare variants might further explain drug response phenotypes in transplantation, and particularly the most severe ones. The advent of next-generation sequencing will help to identify those variants.
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Pouché
authors.affiliation: Laboratory of Chemical Carcinogenesis & Pharmacogenetics, University of Chile, Santiago, Chile.
authors.forename: Jana
authors.initials: J
authors.lastname: Stojanova
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|FHU SUPORT, 87000 Limoges, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.affiliation: Inserm, UMR 850, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|CHU Limoges, Department of Pharmacology, Toxicology & Pharmacovigilance, 2 Avenue Martin-Luther King, F-87042 Limoges, France.|Univ. Limoges, Faculty of Medicine & Pharmacy, 2 rue du Dr Marcland, F-87025 Limoges, France.|FHU SUPORT, 87000 Limoges, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
mesh_terms: D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D000068338:Everolimus / Q000494:pharmacology; D056426:Genetic Loci; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000494:pharmacology; D016377:Organ Transplantation; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011506:Proteins; D016572:Cyclosporine; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: calcineurin; gene polymorphism; inosine monophosphate dehydrogenase; mammalian target of Rapamycin; personalized medicine; pharmacology