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Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: a meta-analysis.
MedLine Citation:
PMID:  22143415     Owner:  NLM     Status:  Publisher    
OBJECTIVE: A systematic review and a meta-analysis were conducted, to investigate the possible association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with adverse effects related to methotrexate (MTX). METHODS: A systematic literature search in PubMed retrieved a total of 44 studies (42 unique articles). Two polymorphisms were included in the meta-analysis: C677T and A1298C. Random effect models were used in the analysis. Odds ratios along with their 95% confidence intervals were computed to compare the distribution of alleles and genotypes between cases and controls. RESULTS: The analysis highlighted a significant association of C677T polymorphism with overall MTX toxicity, hepatotoxicity, hematological toxicity, and neurotoxicity. It also revealed an association with MTX toxicity in patients with rheumatoid arthritis. In contrast, a protective effect of C677T MTHFR polymorphism on acute graft-versus-host disease and on patients treated with hematopoietic cell transplantation was found. As for the A1298C polymorphism, a statistically significant association with overall MTX toxicity and a protective role of the polymorphism in rheumatoid arthritis patients was detected. CONCLUSION: These results indicate the association of MTHFR polymorphisms with MTX toxicity. However, further studies are needed to reveal the underlying biological mechanism of the association.
Kalliopi P Spyridopoulou; Niki L Dimou; Stavros J Hamodrakas; Pantelis G Bagos
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-2
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  -     ISSN:  1744-6880     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
aDepartment of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens bDepartment of Computer Science and Biomedical Informatics, University of Central Greece, Papasiopoulou, Lamia, Greece.
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