en POLSKI
eISSN: 2084-9834
ISSN: 0034-6233
Reumatologia/Rheumatology
Current issue Archive Manuscripts accepted About the journal Supplements Editorial board Reviewers Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank


 
2/2010
vol. 48
 
Share:
Share:
more
 
 
abstract:
Original paper

Effect of methylenetetrahydrofolate reductase polymorphism on toxicity and efficacy of methotrexate in patients with rheumatoid arthritis

Jerzy Świerkot
,
Ryszard Ślęzak
,
Paweł Karpiński
,
Justyna Pawłowska
,
Leszek Noga
,
Jacek Szechiński
,
Piotr Wiland

Reumatologia 2010; 48, 2: 81–93
Online publish date: 2010/05/14
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
Objective: Among patients with rheumatoid arthritis (RA) there is high inter-individual variability in the degree of response to methotrexate (MTX) treatment. One possible cause of the differences in the effectiveness and adverse drug reactions is genetic variation. We evaluated the relationship of C677T and A1298C polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with toxicity and efficacy of MTX in patients with RA.
Material and methods: Genotype analysis of the MTHFR gene was done in 273 Caucasian patients who had been treated with MTX (up to 25 mg per week) and folic acid (5-10 mg per week). All patients had been diagnosed as fulfilling the 1987 ACR criteria. Outcomes were parameters of efficacy of MTX treatment and adverse events. Genomic DNA was obtained from the lymphocytes of peripheral blood. The polymerase chain reaction-restriction fragment length polymorphism assay was applied to determine the genotype of C677T and A1298C polymorphism.
Results: Clinical data of 240 patients with RA treated with MTX were analysed. A good response to therapy was demonstrated in month 6 in 33%, moderate improvement in 43%, and no improvement or deterioration in 24% of patients. 53% of patients described some toxicity during at least one study visit and 16.5% had adverse events leading to MTX withdrawal. Patients with the heterozygous genotype 677CT and homozygous TT genotype exhibited adverse events more frequently than patients with homozygous CC genotype (OR = 1.97, p < 0.01). Furthermore, the MTHFR 677T allele was associated with elevations of aminotransferases (p = 0.02; OR = 3.4). There was no relationship between MTHFR polymorphism and the efficacy of MTX treatment.
Conclusion: MTHFR 677CC polymorphism was associated with a reduction in MTX related adverse effects. This finding indicates that genotyping may help in determining which patients will benefit most from MTX treatment.
keywords:

rheumatoid arthritis, methotrexate, polymorphism, methylenetetrahydrofolate reductase







Quick links
© 2022 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.