Association of MTHF 677TT with adverse drug reactions and RFC G80A with non-response and adverse drug reactions in methotrexate therapy

Being an anti-metabolite and anti-inflammatory agent, Methotrexate, a folate analogue, is indicated for a wide spectrum of diseases including moderate to severe chronic inflammatory disorders like psoriasis and rheumatoid arthritis and malignant diseases such as childhood acute lymphoblastic leukaemia and choriocarcinoma. The outcome of Methotrexate treatment varies. Though up to 50% of patients with inflammatory disorders show a favourable response; one third discontinues Methotrexate due to adverse drug reactions or non-response. Such diversity suggests an inter-individual variation due to multiple factors including genetic polymorphisms. This review was conducted to identify genotypes predictive of Methotrexate treatment outcome. More than 15 alleles located in eight genes were explored by over 25 studies. Among those, we identified MTHFrs1801133TT genotype to be likely associated with adverse drug reactions and RFCrs1051266A allele to be associated with both, non-response and adverse drug reactions. We recommend the conduction of meta-analysis to verify these findings.