• 1
    Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000; 343: 158693.
  • 2
    Van Ede AE, Laan RF, Blom HJ, de Abreu RA, van de Putte LB. Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Semin Arthritis Rheum 1998; 27: 27792.
  • 3
    Ranganathan P, Eisen S, Yokoyama WM, McLeod HL. Will pharmacogenetics allow better prediction of methotrexate toxicity and efficacy in patients with rheumatoid arthritis? Ann Rheum Dis 2003; 62: 49.
  • 4
    Ohosone Y, Okano Y, Kameda H, Hama N, Matsumura M, Nojima T, et al. Toxicity of low-dose methotrexate in rheumatoid arthritis: clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis. Ryumachi 1997; 37: 1623.
  • 5
    Urano W, Taniguchi A, Yamanaka H, Tanaka E, Nakajima H, Matsuda Y, et al. Polymorphisms in the methylenetetrahydrofolate reductase gene were associated with both the efficacy and the toxicity of methotrexate used for the treatment of rheumatoid arthritis, as evidenced by single locus and haplotype analyses. Pharmacogenetics 2002; 12: 18390.
  • 6
    Kumagai K, Hiyama K, Oyama T, Maeda H, Kohno N. Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. Int J Mol Med 2003; 11: 593600.
  • 7
    Berkun Y, Levartovsky D, Rubinow A, Orbach H, Aamar S, Grenader T, et al. Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Ann Rheum Dis 2004; 63: 122731.
  • 8
    Seitz M. Molecular and cellular effects of methotrexate. Curr Opin Rheumatol 1999; 11: 22632.
  • 9
    Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate: increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993; 92: 267582.
  • 10
    Montesinos MC, Yap JS, Desai A, Posadas I, McCrary CT, Cronstein BN. Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine: evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant arthritis. Arthritis Rheum 2000; 43: 65663.
  • 11
    Morabito L, Montesinos MC, Schreibman DM, Balter L, Thompson LF, Resta R, et al. Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5′-nucleotidase-mediated conversion of adenine nucleotides. J Clin Invest 1998; 101: 295300.
  • 12
    Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002; 4: 26673.
  • 13
    Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH. Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis 2001; 60: 72935.
  • 14
    Piper JR, DeGraw JI, Colwell WT, Johnson CA, Smith RL, Waud WR, et al. Analogues of methotrexate in rheumatoid arthritis. II. Effects of 5-deazaaminopterin, 5,10-dideazaaminopterin, and analogues on type II collagen-induced arthritis in mice. J Med Chem 1997; 40: 37784.
  • 15
    Wunder A, Muller-Ladner U, Stelzer EH, Funk J, Neumann E, Stehle G, et al. Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. J Immunol 2003; 170: 4793801.
  • 16
    Neurath MF, Hildner K, Becker C, Schlaak JF, Barbulescu K, Germann T, et al. Methotrexate specifically modulates cytokine production by T cells and macrophages in murine collagen-induced arthritis (CIA): a mechanism for methotrexate-mediated immunosuppression. Clin Exp Immunol 1999; 115: 4255.
  • 17
    Reeves R, D'Eustachio P. Genetic mapping in mice. In: BirrenB, GreenE, HieterP, editors. Genome analysis: a laboratory manual. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1998. p. 71131.
  • 18
    Lander ES, Botstein D. Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 1989; 121: 18599.
  • 19
    Grupe A, Germer S, Usuka J, Aud D, Belknap JK, Klein RF, et al. In silico mapping of complex disease-related traits in mice. Science 2001; 292: 19158.
  • 20
    Smith JD, James D, Dansky HM, Wittkowski KM, Moore KJ, Breslow JL. In silico quantitative trait locus map for atherosclerosis susceptibility in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2003; 23: 11722.
  • 21
    Cronstein BN, Montesinos MC, Weissmann G. Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFκB. Proc Natl Acad Sci U S A 1999; 96: 637781.
  • 22
    Montesinos MC, Desai A, Delano D, Chen JF, Fink JS, Jacobson MA, et al. Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis Rheum 2003; 48: 2407.
  • 23
    Cronstein BN, Naime D, Ostad E. The antiinflammatory effects of methotrexate are mediated by adenosine. Adv Exp Med Biol 1994; 370: 4116.
  • 24
    Schmith VD, Campbell DA, Sehgal S, Anderson WH, Burns DK, Middleton LT, et al. Pharmacogenetics and disease genetics of complex diseases. Cell Mol Life Sci 2003; 60: 163646.
  • 25
    Johnson JA. Pharmacogenetics: potential for individualized drug therapy through genetics. Trends Genet 2003; 19: 6606.
  • 26
    Roses AD. Pharmacogenetics place in modern medical science and practice. Life Sci 2002; 70: 147180.
  • 27
    Krajinovic M, Moghrabi A. Pharmacogenetics of methotrexate. Pharmacogenomics 2004; 5: 81934.
  • 28
    Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 2004; 50: 276674.
  • 29
    Wisniewski HG, Hua JC, Poppers DM, Naime D, Vilcek J, Cronstein BN. TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-α-inhibitor and exerts a strong anti-inflammatory effect in vivo. J Immunol 1996; 156: 160915.
  • 30
    Sud S, Yang SY, Evans CH, Robbins PD, Wooley PH. Effects of cytokine gene therapy on particulate-induced inflammation in the murine air pouch. Inflammation 2001; 25: 36172.
  • 31
    De Leon EJ, Alcaraz MJ, Dominguez JN, Charris J, Terencio MC. A new chloroquinolinyl chalcone derivative as inhibitor of inflammatory and immune response in mice and rats. J Pharm Pharmacol 2003; 55: 131321.
  • 32
    Ospina LF, Calle J, Arteaga L, Pinzon R, Alcaraz MJ, Paya M. Inhibition of acute and chronic inflammatory responses by the hydroxybenzoquinonic derivative rapanone. Planta Med 2001; 67: 7915.
  • 33
    Garcia-Pastor P, Randazzo A, Gomez-Paloma L, Alcaraz MJ, Paya M. Effects of petrosaspongiolide M, a novel phospholipase A2 inhibitor, on acute and chronic inflammation. J Pharmacol Exp Ther 1999; 289: 16672.
  • 34
    Cronstein BN. The mechanism of action of methotrexate. Rheum Dis Clin North Am 1997; 23: 73955.
  • 35
    Andersson SE, Johansson LH, Lexmuller K, Ekstrom GM. Anti-arthritic effect of methotrexate: is it really mediated by adenosine? Eur J Pharm Sci 2000; 9: 33343.
  • 36
    Nesher G, Mates M, Zevin S. Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis. Arthritis Rheum 2003; 48: 5712.
  • 37
    Franco R, Casado V, Ciruela F, Saura C, Mallol J, Canela EI, et al. Cell surface adenosine deaminase: much more than an ectoenzyme. Prog Neurobiol 1997; 52: 28394.
  • 38
    Gorrell MD, Gysbers V, McCaughan GW. CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 2001; 54: 24964.
  • 39
    Lambeir AM, Durinx C, Scharpe S, de Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 2003; 40: 20994.
  • 40
    Hirschhorn R, Ratech H. Isozymes of adenosine deaminase. Isozymes Curr Top Biol Med Res 1980; 4: 13157.
  • 41
    Liani E, Rothem L, Bunni MA, Smith CA, Jansen G, Assaraf YG. Loss of folylpoly-γ-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int J Cancer 2003; 103: 58799.
  • 42
    Rots MG, Pieters R, Peters GJ, Noordhuis P, van Zantwijk CH, Kaspers GJ, et al. Role of folylpolyglutamate synthetase and folylpolyglutamate hydrolase in methotrexate accumulation and polyglutamylation in childhood leukemia. Blood 1999; 93: 167783.
  • 43
    Lyons MA, Wittenburg H, Li R, Walsh KA, Leonard MR, Churchill GA, et al. New quantitative trait loci that contribute to cholesterol gallstone formation detected in an intercross of CAST/Ei and 129S1/SvImJ inbred mice. Physiol Genomics 2003; 14: 22539.
  • 44
    Pitman WA, Korstanje R, Churchill GA, Nicodeme E, Albers JJ, Cheung MC, et al. Quantitative trait locus mapping of genes that regulate HDL cholesterol in SM/J and NZB/B1NJ inbred mice. Physiol Genomics 2002; 9: 93102.
  • 45
    Tabakoff B, Bhave SV, Hoffman PL. Selective breeding, quantitative trait locus analysis, and gene arrays identify candidate genes for complex drug-related behaviors. J Neurosci 2003; 23: 44918.