Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity.
OBJECTIVES: Our study aims to find the relationship between metabolic enzyme thiopurine S-methyltransferase (TPMT) gene polymorphisms and clinical output of the therapy with azathioprine. We focused on patients who experienced leucopenia caused by high blood levels of active azathioprine metabolites.
DESIGN: Our group consists of 87 patients who have been treated by azathioprine. 21 individuals experienced leucopenia during treatment with standard dose of azathioprine. We have used PCR-REA and "real-time" PCR methods for genotype detection G238C, G460G and A719G substitutions in TPMT gene.
RESULTS: We have found statistical association between the presence of non-standard TPMT alleles and adverse event associated with azathioprine treatment - leucopenia (p=0.0033).
CONCLUSION: Our results confirm that TPMT genotyping prior to the treatment with azathioprine could predict patients with genetic predisposition for serious leucopenia and seems to be a useful genetic marker for individualisation of the therapy....
Citation
Kolorz M, Bartosova L, Hosek J, Dvorackova D, Chylkova A, Zboril V, Batovsky M, Bartos M. Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity. Neuro Endocrinol Lett. 2009 Jan; 30(Suppl 1): 137-142