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Will pharmacogenetics allow better prediction of methotrexate toxicity and efficacy in patients with rheumatoid arthritis?
  1. P Ranganathan1,
  2. S Eisen2,
  3. W M Yokoyama3,
  4. H L McLeod4
  1. 1Division of Rheumatology and Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
  2. 2Division of Rheumatology and Department of Medicine, Washington University School of Medicine; and St Louis VA Medical Center, St Louis, Missouri 63106, USA
  3. 3Division of Rheumatology, Department of Medicine, and Howard Hughes Medical Institute, Washington University School of Medicine
  4. 4Departments of Medicine, Molecular Biology and Pharmacology, and Genetics, Washington University School of Medicine
  1. Dr P Ranganathan, Washington University School of Medicine, Division of Rheumatology, 660 S Euclid Avenue, Campus Box 8045, St Louis, MO 63110, USA;


Methotrexate (MTX) remains the most commonly used disease modifying antirheumatic drug in rheumatoid arthritis (RA) because of its cost and experience in its use, despite the availability of new treatments such as leflunomide and the biological agents. However, a significant number of patients with RA either do not benefit from the drug or are unable to tolerate it. Pharmacogenetic approaches may help optimise treatment with MTX, and also other agents, in RA.

  • methotrexate
  • pharmacogenetics
  • rheumatoid arthritis
  • AICAR T′ase, 5-aminoimidazole-4-carboxamide ribonucleotide transformylase
  • ALL, acute lymphoblastic leukaemia
  • CI, confidence interval
  • DHFR, dihydrofolate reductase
  • DMARD, disease modifying antirheumatic drug
  • FPGS, folylpolyglutamate synthase
  • GAR T′ase, glycinamide ribonucleotide transformylase
  • GI, gastrointestinal
  • MTHFR, methylenetetrahydrofolate reductase
  • MTX, methotrexate
  • PCR, polymerase chain reaction
  • RA, rheumatoid arthritis
  • RR, relative risk
  • SAH, S-adenosylhomocysteine
  • SAM, S-adenosylmethionine
  • THF, tetrahydrofolate
  • TYMS, thymidylate synthase

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