The promoter region of the GWAS gene CTLA - 4 (−658 CpG) was found to be hypermethylated in RA individuals, amplifying the aberrant function of regulatory T cells where hypermethylation prevents the binding of the nuclear factor of activated T cells (NF-AT) with a cytoplasmic one, called NF-ATc2, which leads to the decreased expression of the CTLA - 4 gene in RA patients (85). Here, NFATC2 is linked to rheumatoid arthritis.