Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity
Jazyk angličtina Země Švédsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
20027160
PII: NEL300709A23
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
- prohibitiny 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
- Názvy látek
- azathioprin MeSH
- methyltransferasy MeSH
- PHB2 protein, human MeSH Prohlížeč
- prohibitiny MeSH
- thiopurine methyltransferase MeSH Prohlížeč
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.
