Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway

摘要: Methotrexate (MTX) is a disease-modifying anti-rheumatic drug used in the treatment of rheumatoid arthritis (RA). It first line this disease. However, MTX-related adverse reactions (ADRs) are seen 40 % patients. The aim study was to determine impact six genetic polymorphisms located five genes encoding proteins involved MTX metabolic pathway Tunisian RA patients and evaluate its association with toxicity. Genotyping 5,10 methylenetetrahydrofolate reductase (MTHFR C677T A1298C), dihydrofolate (DHFR 19–base pair deletion allele), thymidylate synthase (TYMS 2R/3R), methionine (MTR A2756G) (MTRR A66G) performed using PCR PCR–RFLP method 141 treated MTX. Demographic clinical characteristics were obtained ADRs recorded. Association analyses regard toxicity χ 2 test, toxicogenetic risk index (TRI) Mann–Whitney U-test. analysis highlighted significant T/T genotype MTHFR polymorphism increased A1298C, DHFR 19-base allele, MTR A2756G MTRR A66G not associated TYMS 2R/3R had protective effect against results demonstrated that gene In contrast, overall