title: Measurement of thiopurine methyl transferase activity guides dose-initiation and prevents toxicity from azathioprine.
abstract: OBJECTIVE
  To establish an assay service for thiopurine methyl transferase (TPMT) activity in order to facilitate dose initiation of thiopurine drug therapy and to define appropriate reference intervals and optimal cut-offs for the New Zealand population.
  
  
  METHODS
  407 patients underwent radio-enzymatic assay testing of TPMT activity prior to initiation of thiopurine drug therapy. Those with low activity also underwent genotyping for the abnormal *2, *3A, and *3C alleles.
  
  
  RESULTS
  A trimodal distribution of enzyme activity was seen consistent with the known polymorphic genetics for this enzyme. Three cases of homozygous deficiency were identified. The 'normal' range is 9.3 to 17.6 units/ml red blood cells (RBCs), but many heterozygotes have activity above the lower limit of his range. TPMT activity above 10.7 units/ml RBC identifies a normal genotype with 100% probability.
  
  
  CONCLUSIONS
  The normal range for TPMT has been established. The measurement of TPMT activity helps to guide dose initiation and may prevent toxicity from azathioprine.
authors.affiliation: Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand. chris.sies@cdhb.govt.nz
authors.forename: Christiaan
authors.initials: C
authors.lastname: Sies
authors.forename: Christopher
authors.initials: C
authors.lastname: Florkowski
authors.forename: Peter
authors.initials: P
authors.lastname: George
authors.forename: Richard
authors.initials: R
authors.lastname: Gearry
authors.forename: Murray
authors.initials: M
authors.lastname: Barclay
authors.forename: James
authors.initials: J
authors.lastname: Harraway
authors.forename: Linda
authors.initials: L
authors.lastname: Pike
authors.forename: Trevor
authors.initials: T
authors.lastname: Walmsley
mesh_terms: D001379:Azathioprine / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D015122:Mercaptopurine / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D012016:Reference Values; D013866:Thioguanine / Q000378:metabolism
chemical_list: D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine