Association of FOXP3 Polymorphisms with Susceptibility to Multiple Sclerosis: A Meta-Analysis on Genetic Association Studies

Objectives: FOXP3 is a gene related to regulatory T cells existing on chromosome X. This meta-analysis, based on genetic association studies, was conducted to investigate the association of FOXP3 polymorphisms with susceptibility to multiple sclerosis (MS). Methods: All genetic association studies covering both FOXP3 and multiple sclerosis terms were searched in PubMed, Web of Science and Google Scholar. The information of genotype frequencies was summarized and results were synthesized through odds ratio (OR). Heterogeneity and publication bias were investigated using I2 scale and Begg's funnel plot, respectively. Results: For rs3761548 -3279 C/A polymorphism, AA/AY genotypes were a risk factor in comparison to CC/CY genotypes (P =0.022; OR =1.752; 95% confidence interval [CI] =1.084-2.830; random). AC genotype was a risk factor in comparison to CC/CY genotypes (P =0.004; OR =1.537; 95% CI =1.145-2.062; random) and homozygote genotypes (P =0.016; OR =1.216; 95% CI =1.038-1.426; fixed). For rs2232365 -924 G/A polymorphism, 2 significant associations were found according to a fixed effect model; of course, they did not remain significant in the random effect model. Conclusion: According to the collected populations, susceptibility to and protection from MS are associated with rs3761548 -3279 C/A upstream polymorphism. However, it should be regarded that this association is ethnicity dependent with low effect size.