Investigation of Methylenetetrahydrofolate Reductase Gene Polymorphisms in Patients with Recurrent Aphthous Stomatitis

Background: This study examined whether the methylenetetrahydrofolate reductase (MTHFR) C677T variant was related to recurrent aphthous stomatitis (RAS) and assessed the accompanying hematological and biochemical findings.

Methods: The case–control sample comprised 90 individuals with RAS and 87 unaffected controls who reported no previous oral aphthous ulcers. Participant characteristics were documented, while pain and ulcer severity were quantified with validated assessment tools. Laboratory assessment covered serum iron, ferritin, folate, vitamin B12, and total iron-binding capacity. Genotyping of the C677T locus was performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis.

Results: The proportion of smokers was lower among patients with RAS than among controls (15.6% vs. 41.4%, P < .001), whereas a family history of RAS was reported more often in the patient group (51.1% vs. 20.7%, P < .001). Neither genotype frequencies nor allele distributions showed a between-group difference. Low serum folate was observed in 17.8% of patients and 8.0% of controls (P = .044). Within the RAS cohort, the frequency of low folate varied across genotypes and was highest among TT carriers (44.4%, P = .039). In the adjusted model, gastrointestinal disease (odds ratio [OR] = 3.364, P = .019), a positive family history (OR = 4.516, P < .001), and low serum folate (OR = 5.996, P = .011) were independently related to RAS, while smoking was inversely associated with disease status (OR = 0.249, P = .001).

Conclusion: The results do not support a direct relationship between MTHFR C677T and RAS. In contrast, low folate remained independently associated with the disease, pointing to a possible contribution of altered folate metabolism.