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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2016

Open Access 01-12-2016 | Short Report

Mutations in the MTHFR gene are not associated with Methotrexate intolerance in patients with juvenile idiopathic arthritis

Authors: Andrea Scheuern, Nadine Fischer, Joseph McDonald, Hermine I. Brunner, Johannes-Peter Haas, Boris Hügle

Published in: Pediatric Rheumatology | Issue 1/2016

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Abstract

Background

Methotrexate (MTX) intolerance is a frequent problem of long-term treatment in juvenile idiopathic arthritis (JIA). Mutations in the methylentetrahydrofolate reductase (MTHFR) gene may increase toxicity of MTX, potentially constituting an initial stimulus for this conditioned response. The objective of this study was to investigate the relationship of common MTHFR gene mutations and occurrence of MTX intolerance in pediatric patients with JIA treated with MTX.

Methods

Consecutive JIA patients on at least 3 months of MTX treatment were included in this study. Intolerance to MTX was determined using the Methotrexate Intolerance Severity Score (MISS) questionnaire, and MTX intolerance was defined as MISS values of ≥ 6. Presence of the two most common mutations in the MTHFR gene (C677T and A1298C) was tested using a PCR assay. Results were analyzed using descriptive and non-parametric statistics.

Results

196 patients were included (73 % female). Of those, 93 (46 %) showed MTX intolerance. 168 patients were genotyped for C677T and A1298C. MTX intolerance was not found to be significantly more frequent among patients with hetero- and homozygous or homozygous mutations C677T or A1298C compared to wild type or heterozygous mutations. Analysis of the correlation between numbers of mutations in these two loci to the MISS score did not yield a statistically significant correlation.

Conclusion

Mutations in the MTHFR gene were not found to be significantly more frequent in JIA patients intolerant to MTX. Toxicity associated with the MTHFR gene seems to result from mechanisms different to those involved in clinical MTX intolerance.
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Metadata
Title
Mutations in the MTHFR gene are not associated with Methotrexate intolerance in patients with juvenile idiopathic arthritis
Authors
Andrea Scheuern
Nadine Fischer
Joseph McDonald
Hermine I. Brunner
Johannes-Peter Haas
Boris Hügle
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2016
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-016-0071-y

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