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Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity
M. Kolorz, L. Bartosova, J. Hosek, D. Dvorackova, A. Chylkova, V. Zboril, M. Batovsky, M. Bartos
Jazyk angličtina Země Švédsko
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NR9342
MZ0
CEP - Centrální evidence projektů
PubMed
20027160
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- azathioprin škodlivé účinky krev MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- leukopenie chemicky indukované MeSH
- lidé MeSH
- methyltransferasy genetika MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus genetický MeSH
- sekvenční analýza DNA MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
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- $a Kolorz, Michal. $7 _BN006015 $u Department of Human Pharmacology and Toxicology, University of Veterinary and Pharmaceutical Sciences Brno,, Czech Republic. michalkolorz@seznam.cz
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- $a Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity / $c M. Kolorz, L. Bartosova, J. Hosek, D. Dvorackova, A. Chylkova, V. Zboril, M. Batovsky, M. Bartos
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- $a 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.
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