Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation.

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dc.contributor.authorAggarwal, Parshanten_US
dc.contributor.authorNaik, Sitaen_US
dc.contributor.authorMishra, K Pen_US
dc.contributor.authorAggarwal, Amitaen_US
dc.contributor.authorMisra, Ramnathen_US
dc.date.accessioned2006-11-11en_US
dc.date.accessioned2009-05-27T06:35:49Z
dc.date.available2006-11-11en_US
dc.date.available2009-05-27T06:35:49Z
dc.date.issued2006-11-11en_US
dc.description.abstractBACKGROUND & OBJECTIVES: C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity of methotrexate (MTX). We studied the relationship between the C677T gene polymorphism and toxicity and efficacy of MTX in patients with rheumatoid arthritis (RA) on folate supplementation. METHODS: A total of 150 RA patients fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/- 20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction enzyme method. Primary endpoint for treatment efficacy was change in disease activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood count, renal and liver function tests and a standardized questionnaire. RESULTS: The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic acid supplementation. Forty two per cent (63/150) of the patients had C677T polymorphism of which 4 were homozygous (T/T) and 59 were heterozygous (C/T). The baseline characteristics of the patients with or without polymorphism were comparable. The frequency of adverse events was not increased in patients with C677T polymorphism with 11 patients experiencing adverse events as compared to 19 in the group without polymorphism (of whom 4 and 7 patients respectively discontinued treatment). The C677T polymorphism was not associated with any difference in response to treatment. INTERPRETATION & CONCLUSION: Our findings suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity or efficacy of MTX treatment in RA patients receiving folate supplementation. Further studies need to be done to look at polymorphisms in other enzymes that may have association with MTX clinical efficacy and toxicity.en_US
dc.description.affiliationDepartment of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, India.en_US
dc.identifier.citationAggarwal P, Naik S, Mishra KP, Aggarwal A, Misra R. Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation. Indian Journal of Medical Research. 2006 Nov; 124(5): 521-6en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/17012
dc.language.isoengen_US
dc.source.urihttps://icmr.nic.in/ijmr/ijmr.htmen_US
dc.subject.meshAdulten_US
dc.subject.meshAntirheumatic Agents --therapeutic useen_US
dc.subject.meshArthritis, Rheumatoid --drug therapyen_US
dc.subject.meshFemaleen_US
dc.subject.meshFolic Acid --administration & dosageen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMethotrexate --adverse effectsen_US
dc.subject.meshMethylenetetrahydrofolate Reductase (NADPH2) --geneticsen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshPolymorphism, Geneticen_US
dc.titleCorrelation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation.en_US
dc.typeJournal Articleen_US
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