Identification of thiopurine methyltransferase (TPMT) polymorphisms cannot predict myelosuppression in systemic lupus erythematosus patients taking azathioprine.
OBJECTIVE
To determine whether the presence of polymorphisms associated with reduced or absent activity of thiopurine methyltransferase (TPMT), an enzyme involved in azathioprine metabolism, can predict side-effects, particularly myelosuppression, in patients taking this drug.


METHODS
The TPMT genotype was determined in 120 patients with systemic lupus erythematosus (SLE) together with 15 patients with inflammatory bowel disease (IBD) and correlated with the effects of clinical exposure to azathioprine.


RESULTS
TPMT polymorphisms were detected in eight patients. Severe marrow toxicity occurred in the single homozygote identified. Azathioprine was generally well tolerated, but 11 drug-associated neutropenias were detected. In only one of the 11 cases was a TPMT polymorphism identified.


CONCLUSIONS
Homozygous TPMT deficiency was associated with severe marrow suppression. In the majority of cases, however, TPMT genotyping prior to azathioprine therapy would not have predicted myelosuppressive events and may augment, but not replace, regular blood monitoring.
Naughton
M A
MA
Imperial College of Science and Medicine, Rheumatology Section, London, UK.
Battaglia
E
E
O'Brien
S
S
Walport
M J
MJ
Botto
M
M
D001379:Azathioprine / Q000009:adverse effects*; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000201:enzymology; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D009503:Neutropenia / Q000139:chemically induced; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine