title: Pharmacogenetic significance of inosine triphosphatase.
abstract: Inosine triphosphatase (ITPase) is the enzyme that catalyzes the conversion of inosine triphosphate (ITP) and deoxy-inosine triphosphate (dITP) to inosine monophosphate and deoxy-inosine monophosphate, respectively, thereby maintaining low intracellular concentrations of ITP and dITP. Individuals deficient in ITPase activity were first recognized over 30 years ago. For decades, no clinical significance could be attributed to this inborn error of metabolism whatsoever. In recent years, evidence has started to accumulate that polymorphisms in the gene encoding ITPase are associated with potentially severe adverse drug reactions towards the thiopurine drugs azathioprine and 6-mercaptopurine. The pharmacogenetic significance is presently being debated in the literature. However, the present state of knowledge is still insufficient to definitively determine the pharmacogenetic significance of ITPase. This article aims to review the current knowledge on the role of ITPase in thiopurine metabolism.
authors.affiliation: Maastricht University Hospital, Laboratory of Biochemical Genetics, Department of Clinical Genetics, PO Box 6202 AZ Maastricht, The Netherlands. jorgen.bierau@gen.unimaas.nl
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bierau
authors.forename: Martijn
authors.initials: M
authors.lastname: Lindhout
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Bakker
mesh_terms: D014644:Genetic Variation; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000172:deficiency* / Q000235:genetics*; D000097630:Inosine Triphosphatase
chemical_list: D011755:Pyrophosphatases; D000097630:Inosine Triphosphatase