The rs3761548 FOXP3 variant is associated with multiple sclerosis and transforming growth factor β1 levels in female patients

Objective The aim of this study was to evaluate the association between rs3761548 FOXP3 (-3279 C > A) variant and multiple sclerosis (MS), disability, disability progression, as well as transforming growth factor (TGF)-beta 1 and interleukin (IL)-10 plasma levels in MS patients. Methods and subjects The study included 170 MS patients and 182 controls. Disability was evaluated using Expanded Disability Status Scale (EDSS) and categorized as mild (EDSS <= 3) and moderate/high (EDSS > 3). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS). The rs3761548 variant was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Plasma levels of TGF-beta 1 and IL-10 were determined using immunofluorimetric assay. Results CA and AA genotypes were associated with MS [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.66-3.53, p = 0.012; OR 8.19, 95% CI 3.04-22.07, p < 0.001, respectively). With the dominant model, the CA+AA genotypes were associated with MS (OR 2.57, 95% CI 1.50-4.37, p < 0.001). In the recessive model, the AA genotype was also associated with MS (OR 5.38, 95% CI 2.12-13.64, p < 0.001). After adjustment by age, ethnicity, BMI and smoking, all these results remained significant, as well as female patients carrying the CA+AA genotypes showed higher TGF-beta 1 than those carrying the CC genotype (OR 1.35, 95% CI 1.001-1.054, p = 0.043). No association was observed between the genotypes and disability, disability progression and IL-10 levels. Conclusion These results suggest that the A allele of FOXP3 -3279 C > A variant may exert a role in the T regulatory cell function, which could be one of the factors involved in the susceptibility for MS in females.