Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single‐nucleotide polymorphisms in genes coding for folate pathway enzymes

摘要: Objective To determine associations of methotrexate (MTX) efficacy and toxicity with single-nucleotide polymorphisms (SNPs) in genes coding for folate pathway enzymes patients early rheumatoid arthritis (RA). Methods Patients (n = 205) active RA received MTX at an initial dosage 7.5 mg/week, which was increased to 15 mg/week combined folic acid (1 mg/day) after 4 weeks. If the Disease Activity Score 44 joints (DAS44) >2.4 3 months, 25 mg/week. evaluated 6 months compared genotypes analyses: without good response (DAS44 ≤2.4), improvement (ΔDAS44 >1.2), moderate >0.6). The association between MTX-related adverse drug events (ADEs) genotype by comparing ADEs, specifically pneumonitis, gastrointestinal skin mucosal elevated liver enzyme levels. following SNPs were analyzed: methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, dihydrofolate (DHFR) −473G>A, DHFR 35289G>A, reduced carrier 80G>A. In case significant differences, odds ratios (ORs) calculated. Results At 1298AA associated relative 1298C (OR 2.3, 95% confidence interval [95% CI] 1.18–4.41), copies 677CC haplotype. contrast, allele carriers developed more ADEs 2.5, CI 1.32–4.72). Conclusion Patients showed greater clinical MTX, whereas only toxicity. future, may help will benefit most from treatment.