Background: Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease that can cause swelling and damage the cartilage and bone around the joints. Some factors such as polymorphic variations of the HLA-DRB1 and MTHFR genes have been identified as potential markers of susceptibility, severity, or protection in RA. In this disorder, hands and feet are the most affected parts of the body. The risk of RA is almost three times higher in women than in men, and the onset of RA is more common between 40 and 60 years of age, but the disease may occur at any age.

Objectives: To study the possible association between the MTHFR C677T polymorphism and RA risk in the Khuzestan province.

Patients and Methods: The study included 240 persons (120 patients with RA and 120 healthy controls). Genomic DNA was isolated and genotyping was performed by restriction-fragment-length-polymorphism (PCR-RFLP)-based assays.

Results: Our results showed significant differences between the groups with respect to MTHFR C677T genotype (P = 0.015) and allele frequencies (0.004). Statistical analysis showed that there is no relation between gender, age, and RA risk. However, we found that there is a significant association between ethnicity and the risk of RA (P < 0.001). After examining the clinical factors, levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), separately from genotype frequencies, we found that there is no difference between these factors and MTHFR C677T genotypes. However, comparison of RF and anti-CCP with one another, showed significant association (P = 0.001). There was no significant deviation in frequencies of the MTHFR C677T polymorphism from Hardy-Weinberg equilibrium for the patient and control groups (P > 0.05).

Conclusions: Our findings suggest that there is an association between the MTHFR C677T polymorphism and susceptibility for the development of RA.