The Frequency of A1298C and C677T Polymorphisms of the Methylentetrahydrofolate Gene in Turkish Patients with Rheumatoid Arthritis: Relationship with Methotrexate Toxicity

Özgür Taşbaş1, Pınar Borman*, 1, Halil Gürhan Karabulut2, Ajlan Tükün2, Rezan Yorgancıoğlu1
1 Ankara Training and Research Hospital I. Clinic of Physical Medicine and Rheumatology, Cebeci, Ankara, Turkey
2 University of Ankara, Faculty of Medicine, Dept of Genetics, Sıhhiye, Ankara, Turkey

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© Taşbaş et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Birlik Mahallesi Zirvekent Mimoza Sitesi, A-1 Blok No: 59, Çankaya, Ankara, Turkey; Tel: 90.5324649897; E-mail:


The C677T and A1298C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine the frequency of MTHFR C677 T and A1298C gene polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity.

Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ±12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and MTX-related adverse effects were recorded in the patient group. The A1298C and C677T polymorphisms of the MTHFR gene were analyzed and the distribution of genotypes according side effects, were determined.

The frequency of MTHFR C677T and A1298C polymorphisms were similar in the patient and control groups. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment, and MTX had been discontinued in 12 (18.8%) patients due to side effects and/or inefficacy. MTHFR C677T and A1298C gene polymorphisms were found to be similar in patients with and without MTX-related adverse events.

In conclusion, A1298C and C677T polymorphisms in the MTHFR gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA.

Keywords: Rheumatoid arthritis, methotrexate, MTHFR gene, A1298C polymorphism, C677T polymorphism, folate..