Association between biotin deficiency and FOXP3 gene polymorphism (rs3761548) in patients with rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a common inflammatory disease characterized by synovial tissue swelling and inflammation that results in joint destruction and dysfunction. This study was a first evaluation of serum biotin levels in patients with RA and the relationships with disease activity score (DAS28). The current study aimed to determine whether there is a deficiency in serum biotin concentration, to explore its relationship with disease severity, and to investigate whether the polymorphism in the forkhead box P3 ( FOXP3 ) gene (rs3761548) is a risk factor among patients with RA and if this polymorphism influences serum biotin concentration. Materials and methods This case-control study involved the examination of 136 RA patients and 85 as a control group. Serum biotin concentration was measured by Enzyme-Linked Immunosorbent Assay (ELISA), DNA sequencing was performed by Sanger sequencing, and the DAS28 was also evaluated for all patients. Results The serum biotin levels in the control group were significantly higher than those in the patient group ( p -value: <0.001). A statistically significant difference in biotin levels was observed across disease severity groups according to DAS28/ESR ( p -value = 0.034) and DAS28/CRP ( p -value = 0.021). The A allele of rs3761548 in the FOXP3 gene was significantly more prevalent among Iraqi RA patients ( p -value = 0.001). Genetic polymorphism (rs3761548) significantly influences serum biotin concentrations ( p -value = 0.019). Conclusions The study findings support a pathophysiological role for biotin deficiency in RA, with reduced serum biotin levels associated with increased disease severity. Under the recessive genetic model, the FOXP3 (rs3761548) AA genotype was identified as a significant risk factor for RA susceptibility and was associated with elevated DAS28 scores, reflecting higher disease activity among carriers. Interestingly, the AA genotype was also associated with higher serum biotin concentrations, indicating that rs3761548 exerts a significant influence on circulating biotin levels. These findings suggest a complex interplay between genetic variation in FOXP3 and biotin metabolism in the pathogenesis of RA, warranting further mechanistic investigation into this relationship and its potential clinical implications.