Document Detail


Associations between the C677T and A1298C polymorphisms of MTHFR and the efficacy and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis.
MedLine Citation:
PMID:  20067328     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND OBJECTIVE: The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene have been reported to be associated with the toxicity and efficacy of methotrexate in rheumatoid arthritis (RA), although the results of previous studies have been inconsistent. The aim of this study was to explore whether the C677T and A1298C polymorphisms of MTHFR play a role in the toxicity and efficacy of methotrexate in RA. METHODS: The authors identified and evaluated studies conducted on the association between the C677T and A1298C polymorphisms of MTHFR and on the toxicity and efficacy of methotrexate in RA. A meta-analysis was then conducted to compare the toxicity and efficacy of methotrexate with respect to the 677CC and 677CT/TT genotypes and the 1298AA and 1298AC/CC genotypes. RESULTS: Eight studies, which included a total of 1514 patients with RA, were included in this meta-analysis. Meta-analysis did not show any association between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in RA in all patients or in Asian patients. The odds ratios (ORs) for adverse effects with 677CC versus 677CT/TT in all patients and in Asian patients were 0.633 (95% CI 0.325, 1.234; p = 0.180) and 0.621 (95% CI 0.233, 1.655; p = 0.341), respectively. The ORs for adverse effects with 1298AA versus 1298AC/CC in all patients and in Asian patients were 0.942 (95% CI 0.479, 1.851; p = 0.861) and 0.978 (95% CI 0.569, 1.681; p = 0.936), respectively. Heterogeneities were evident among the included studies. In addition, no association was found between the C677T and A1298C polymorphisms and the efficacy of methotrexate in RA in all patients. CONCLUSIONS: Our meta-analysis including 1514 patients with RA found no association between the C677T and A1298C polymorphisms of MTHFR and the toxicity and efficacy of methotrexate in RA. Because of the paucity of pharmacogenetic data, further studies are needed to determine the role of MTHFR polymorphisms in the toxicity and efficacy of methotrexate.
Authors:
Young Ho Lee; Gwan Gyu Song
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Clinical drug investigation     Volume:  30     ISSN:  1173-2563     ISO Abbreviation:  Clin Drug Investig     Publication Date:  2010  
Date Detail:
Created Date:  2010-01-13     Completed Date:  2010-04-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9504817     Medline TA:  Clin Drug Investig     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  101-8     Citation Subset:  IM    
Affiliation:
Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, 126-1 5-ga, Anam-dong, Seongbuk-gu, Seoul, 136-705, Korea. lyhcgh@korea.ac.kr
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Antirheumatic Agents / adverse effects*,  therapeutic use*
Arthritis, Rheumatoid / drug therapy*,  pathology
Humans
Methotrexate / adverse effects*,  therapeutic use*
Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
Polymorphism, Genetic
Publication Bias
Chemical
Reg. No./Substance:
0/Antirheumatic Agents; 59-05-2/Methotrexate; EC 1.5.1.20/Methylenetetrahydrofolate Reductase (NADPH2)

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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