RESEARCH - MTX related adverse effects in patients with RA are associated with the A1298C polymorphism of the MTHFR gene

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Ann Rheum Dis. 2004 Oct;63(10):1227-31.

Methotrexate related adverse effects in patients with rheumatoid

arthritis are associated with the A1298C polymorphism of the MTHFR gene.

Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, Abou

Atta I, Mevorach D, Friedman G, Ben-Yehuda A.

Department of Paediatrics, Bikur Cholim General Hospital, POB 492,

Jerusalem 91004, Israel. berkun@...

BACKGROUND: There is an association between C677T polymorphism of the

methylenetetrahydrofolate reductase (MTHFR) gene and methotrexate

related toxicity. OBJECTIVE: To examine the relations between the

recently described A1298C polymorphism of the MTHFR gene, plasma

homocysteine, methotrexate toxicity, and disease activity in patients

with rheumatoid arthritis. DESIGN: A cross sectional study on 93

methotrexate treated patients with rheumatoid arthritis, comprising a

clinical interview and physical examination to determine disease

activity and methotrexate related adverse reactions. Genotype analysis

of the MTHFR gene was carried out and fasting plasma homocysteine and

serum folate concentrations were measured. The data were analysed using

univariate analysis. Allele and genotype distributions were compared

with those of a healthy control group. RESULTS: The frequency of the

1298CC genotype (24.7%) in the rheumatoid study group was greater than

expected in the general population (12.8%, p<0.001). This genotype was

associated with a significantly low rate of methotrexate related side

effects. The odds ratio for side effects in patients with wild type

1298AA genotype v 1298CC genotype was 5.24 (95% confidence interval,

1.38 to 20). No correlation of disease activity variables or plasma

homocysteine with MTHFR A1298C and C677T polymorphisms was observed.

CONCLUSIONS: 1298CC polymorphism was more common in methotrexate treated

rheumatoid patients than expected in the population, and was associated

with a reduction in methotrexate related adverse effects. The A1298C

polymorphism of the MTHFR gene may indicate a need to adjust the dose of

methotrexate given to patients with rheumatoid arthritis.

PMID: 15361376

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5361377 & dopt=Abstract

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