title: Update on thiopurine pharmacogenetics in inflammatory bowel disease.
abstract: Azathioprine and 6-mercaptopurine remain pivotal therapies for the maintenance of disease remission in patients with Crohn's disease and ulcerative colitis. While thiopurine S-methyltransferase deficiency was the first pharmacogenetic phenomenon to be recognized to influence thiopurine toxicity and reliably predict leukopenia, it does not predict other adverse effects, nor does it explain most cases of thiopurine resistance. In recent years, a number of other genetic polymorphisms have received increasing attention in the literature. In particular, SNPs in NUDT15 and in the class II HLA locus have been shown to predict thiopurine-related leukopenia and pancreatitis. The aim of this review is to provide a concise update of genetic variability which may influence patient response to azathioprine and 6-mercaptopurine.
authors.affiliation: Department of Surgical Sciences, Dunedin School of Medicine, PO Box 56, Dunedin, New Zealand.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Roberts
authors.affiliation: Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch, New Zealand.|Department of Gastroenterology, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand.
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics; D004342:Drug Hypersensitivity / Q000235:genetics / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000235:genetics; D015122:Mercaptopurine / Q000627:therapeutic use; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000235:genetics / Q000473:pathology; D011755:Pyrophosphatases / Q000235:genetics; D000096964:Nudix Hydrolases
chemical_list: D001379:Azathioprine; D000949:Histocompatibility Antigens Class II; D015122:Mercaptopurine; D011755:Pyrophosphatases; C543721:NUDT15 protein, human; D000096964:Nudix Hydrolases
keywords: 6-MMP; 6-TGN; 6-mercaptopurine; NUDT15; RAC1; TPMT; azathioprine; polymorphism