Methylene tetrahydrofolate reductase genotype and homocysteine levels: association with rheumatoid arthritis

Background. Methylenetetrahydrofolate reductase (MTHFR) is necessary for maintaining folate homeostasis. When MTHFR function is impaired, homocysteine levels increase, augmenting the release of pro-inflammatory cytokines that are attributed to the etiology of rheumatoid arthritis (RA). Objectives. To assess the association of the MTHFR gene variant (C677T rs1801133) and homocysteine level in patients with RA. Methods. This case-control study was conducted on 88 subjects, 44 patients with RA diagnosed based on the American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) 2010 RA classification criteria, and 44 healthy controls. Serum homocysteine levels were measured using enzyme-linked immunosorbent assay (ELISA), and genotyping for MTHFR C677T polymorphism (rs1801133) was done by allelic discrimination PCR assay. Logistic regression was used to determine the most independent risk factor. Results. Serum homocysteine level was significantly increased in the RA patients compared to controls (p < 0.001). The CT genotype of MTHFR C677T polymorphism was significantly more frequent among RA patients (54.5%) compared to controls (31.8%) (p = 0.013), with an odds ratio (OR) of 3.107 (95% CI: 1.265–7.630). In addition, the T allele was significantly more frequent in patients (36.4%) than controls (18.2%) (p = 0.008), with an OR of 2.571 (95% CI: 1.284–5.149). Homocysteine level had a significant positive correlation with Disease Activity Score 28 (DAS28) and CRP (p < 0.001, p = 0.006). Multivariate regression analysis revealed that homocysteine level and dominant genotype model (GA+AA) independently contribute to the risk of RA. Conclusion. MTHFR C677T polymorphism is associated with rheumatoid arthritis, along with homocysteine level, which may be a useful marker for RA disease activity.