Measurement of thiopurine methyl transferase activity guides dose-initiation and prevents toxicity from azathioprine.
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.
Sies
Christiaan
C
Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand. chris.sies@cdhb.govt.nz
Florkowski
Christopher
C
George
Peter
P
Gearry
Richard
R
Barclay
Murray
M
Harraway
James
J
Pike
Linda
L
Walmsley
Trevor
T
D001379:Azathioprine / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D015122:Mercaptopurine / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism*; D012016:Reference Values; D013866:Thioguanine / Q000378:metabolism
D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine; D001379:Azathioprine