Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity.
OBJECTIVE
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.


METHODS
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).


CONCLUSIONS
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.
Kolorz
Michal
M
Department of Human Pharmacology and Toxicology, University of Veterinary and Pharmaceutical Sciences Brno,, Czech Republic. michalkolorz@seznam.cz
Bartosova
Ladislava
L
Hosek
Jan
J
Dvorackova
Dana
D
Chylkova
Alicja
A
Zboril
Vladimir
V
Batovsky
Marian
M
Bartos
Milan
M
D000328:Adult; D000483:Alleles; D001379:Azathioprine / Q000009:adverse effects* / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000091402:Prohibitins; D017422:Sequence Analysis, DNA
C000717331:PHB2 protein, human; D000091402:Prohibitins; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine