Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms are Not Associated With Recurrent Aphthous Stomatitis: A Case-Control Study

Objectives Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been investigated as potential genetic factors associated with recurrent aphthous stomatitis (RAS). This study investigated whether MTHFR C677T and A1298C polymorphisms, as well as circulating homocysteine, folate, and vitamin B12 levels, are associated with RAS. Materials and methods In this prospective case-control study, 55 patients with clinically diagnosed RAS and 55 age- and sex-matched controls were enrolled. MTHFR C677T and A1298C genotyping was performed by polymerase chain reaction on genomic DNA extracted from EDTA blood samples. Plasma homocysteine was measured by chemiluminescent immunoassay, while serum folate and vitamin B12 were assessed by electrochemiluminescence. In patients with RAS, number of ulcers, clinical subtype, episode frequency, healing time, and pain intensity were recorded. Associations were analysed using χ ² tests and ANOVA, with statistical significance set at P < .05. Results No significant differences were found between RAS and non-RAS groups in the distribution of MTHFR C677T or A1298C genotypes. Mean homocysteine, folate, and vitamin B12 levels, as well as their categorical distributions, were also comparable between groups (all P > .05). Within the RAS group, episode frequency was significantly associated with homocysteine and folate serological levels, whereas no significant associations were observed between MTHFR genotypes and the clinical variables assessed. Conclusions In this cohort, MTHFR C677T and A1298C polymorphisms were not associated with RAS occurrence. However, homocysteine and folate serological levels were associated with selected indicators of disease course, suggesting that metabolic factors may contribute to RAS phenotype in a subset of patients. Clinical relevance Although MTHFR polymorphisms do not appear to be directly associated with RAS onset, assessment of homocysteine and folate serological levels may help identify patients with a more severe or recurrent clinical course and support a more individualized approach.