Importance of thiopurine S-Methyltransferase gene polymorphisms for prediction of azathioprine toxicity
Language English Country Sweden Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20027160
PII: NEL300709A23
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- Azathioprine adverse effects blood MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Genotype MeSH
- Polymorphism, Single Nucleotide MeSH
- Leukopenia chemically induced MeSH
- Humans MeSH
- Methyltransferases genetics MeSH
- Polymerase Chain Reaction MeSH
- Polymorphism, Genetic * MeSH
- Prohibitins MeSH
- Sequence Analysis, DNA MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Azathioprine MeSH
- Methyltransferases MeSH
- PHB2 protein, human MeSH Browser
- Prohibitins MeSH
- thiopurine methyltransferase MeSH Browser
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.
