SNPs in AIF-136, ESR a (ESR1) and ESR b (ESR2)37, PTPN2238, HLA-DRB1 and HLA-DQB139, TGFB140, TLR440, CXCL9 and CXCL1041 have been evaluated, although most of these studies showed a negative association between these polymorphisms and MTX effectiveness in RA patients with the exception of the AIF1 CC (rs2259571) genotype, which showed a poorer response to therapy with MTX36, and HLA-DRB1*03, which Ali AA et al. 39 found to be significantly associated with nonresponders to MTX treatment, and suggested that Pakistani patients with this genotype are less likely to benefit from MTX. This evidence concerns the gene ESR2 and rheumatoid arthritis.