ATIC and rheumatoid arthritis: Several explanations can be proposed for such observed discrepancies, such as bias related to study design and settings, sample size/power, ethnicity, the population disease duration (early or established RA), changes in folate status, influence of less common single nucleotide polymorphisms (SNPs) in MTHFR and ATIC, polymorphisms in genes encoding to other intervenient proteins in folate, purine, pyrimidine, adenosine, and methionine pathways, and also differences in the definition of MTX clinical response [28].