Skip to main content
SpringerLink
Log in

Pharmacogenomics in Rheumatoid Arthritis

  • Protocol
Pharmacogenomics in Drug Discovery and Development

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 448))

Summary

Rheumatoid arthritis (RA) is a systemic inflammatory arthritis that leads to severe joint damage and is associated with high morbidity and mortality. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs not only relieve the clinical signs and symptoms of RA but also inhibit the radiographic progression of disease. Recently, a new class of disease-modifying medications, the biologic agents, has been added to the existing spectrum of DMARDs in RA. However, patients' response to these agents is not uniform, with considerable variability in both efficacy and toxicity. There are no reliable means of predicting an individual patient's response to a given DMARD prior to initiation of therapy. In this chapter, the current published literature on the pharmacogenomics of traditional DMARDs and the newer biologic DMARDs in RA is highlighted. Pharmacogenomics may help individualize drug therapy in patients with RA in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pincus, T., Callahan, L. F., Sale, W. G., Brooks, A. L., Payne, L. E., and Vaughn, W.K. (1984) Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis and Rheumatism. 8, 864–872.

    Article  Google Scholar 

  2. Weinblatt, M. E., Coblyn, J. S., Fox, D. A., et al. (1985) Efficacy of low-dose methotrexate in rheumatoid arthritis. N England Journal of Medicine. 312, 818–822.

    Article  CAS  Google Scholar 

  3. Kremer, J.M., and Phelps, C.T. (1992) Long-term prospective study of the use of methotrexate in the treatment of rheumatoid arthritis. Update after a mean of 90 mo. Arthritis and Rheumatism. 35, 138–145.

    Article  CAS  PubMed  Google Scholar 

  4. Kremer, J. M. (2001) Rational use of new and existing disease-modifying agents in rheumatoid arthritis. Annals of Internal Medicine. 134, 695–706.

    CAS  PubMed  Google Scholar 

  5. Strand, V., Cohen, S., Schiff, M., et al. (1999) Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Archives of Internal Medicine. 159, 2542–2550.

    Article  CAS  PubMed  Google Scholar 

  6. Bathon, J.M., Martin, R.W., Fleischmann, R.M., et al. (2001) A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. New England Journal of Medicine. 343, 1586–1593.

    Article  Google Scholar 

  7. Hooijberg, J.H., Broxterman, H.J., Kool, M., et al. (1999) Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Research. 59, 2532–2535.

    CAS  PubMed  Google Scholar 

  8. Galivan, J. (1980) Evidence for the cytotoxic activity of polyglutamate derivatives of methotrexate. Molecular Pharmacology. 17, 105–110.

    CAS  PubMed  Google Scholar 

  9. van Ede, A.E., Laan, R.F., Blom, H.J., De Abreu, R.A., and van de Putte, L.B. (1998) Methotrexate in rheumatoid arthritis: an update with focus on mechanisms involved in toxicity. Seminars in Arthritis and Rheumatism. 27, 277–292.

    Article  PubMed  Google Scholar 

  10. Szeto, D.W., Cheng, Y.C., Rosowsky, A., t al. (1979) Human thymidylate synthetase–III. Effects of methotrexate and folate analogs. Biochemical Pharmacology. 28, 2633–2637.

    Article  CAS  PubMed  Google Scholar 

  11. Chan, E.S., and Cronstein, B.N. (2002) Molecular action of methotrexate in inflammatory diseases. Arthritis Research. 4, 266–273.

    Article  PubMed  Google Scholar 

  12. Rothem, L., Aronheim, A., and Assaraf, Y.G. (2003) Alterations in the expression of transcription factors and the reduced folate carrier as a novel mechanism of antifolate resistance in human leukemia cells. Journal of Biological Chemistry. 278, 8935–8941.

    Article  CAS  PubMed  Google Scholar 

  13. Rothem, L., Stark, M., Kaufman, Y., Mayo, L., and Assaraf, Y.G. (2004) Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. Journal of Biological Chemistry. 279, 374–384.

    Article  CAS  PubMed  Google Scholar 

  14. Whetstine, J.R., Witt, T.L., and Matherly, L.H. (2002) The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism. Journal of Biological Chemistry. 277, 43873–43880.

    Article  CAS  PubMed  Google Scholar 

  15. Dervieux, T., Lein, D.O., Park, G., et al. (2003) Single nucleotide polymorphisms in the folate/ purine synthesis pathway predict methotrexate's effects in rheumatoid arthritis [abstract]. Arthritis and Rheumatism. 48(suppl. 9), S438.

    Google Scholar 

  16. Hoffmeyer, S., Burk, O., von Richter, O., et al. (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proceedings of the National Academy of Sciences of the United States of America. 97, 3473–3478.

    Article  CAS  PubMed  Google Scholar 

  17. Kim, R.B., Leake, B.F., Choo, E.F., et al. (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clinical Pharmacology and Therapeutics. 70, 189–199.

    Article  CAS  PubMed  Google Scholar 

  18. Tanabe, M., Ieiri, I., Nagata, N., et al. (2001) Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. Journal of Pharmacology and Experimental Therapeutics. 297, 1137–1143.

    CAS  PubMed  Google Scholar 

  19. Norris, M.D., De Graaf, D., Haber, M., et al. (1996) Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. International Journal of Cancer. 65, 613–619.

    Article  CAS  Google Scholar 

  20. Mickisch, G.H., Merlino, G.T., Galski, H., Gottesman, M.M., and Pastan, I. (1991) Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance. Proceedings of the National Academy of Sciences of the United States of America. 88, 547–551.

    Article  CAS  PubMed  Google Scholar 

  21. Hider, S. L., Morgan, C., Bell, E., and Bruce, I. N. (2002) Methotrexate is not a substrate for P-glycoprotein in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 61(suppl. 1), 199.

    Google Scholar 

  22. Pawlik, A., Wrzesniewska, J., Fiedorowicz-Fabrycy, I., Gawronska- and Szklarz, B. (2004) The MDR1 3435 polymorphism in patients with rheumatoid arthritis. International Journal of Clinical Pharmacology and Therapeutics. 42, 496–503.

    CAS  PubMed  Google Scholar 

  23. Rozen, R. (1996) Molecular genetics of methylenetetrahydrofolate reductase deficiency. Journal of Inherited Metabolic Disease. 19, 589–594.

    Article  CAS  PubMed  Google Scholar 

  24. Frosst, P., Blom, H.J., Milos, R., et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genetics. 10, 111–113.

    Article  CAS  PubMed  Google Scholar 

  25. van der Put, N. M., Gabreels, F., Stevens, E. M., et al. (1998) A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? American Journal of Human Genetics. 62, 1044–1051.

    Article  PubMed  Google Scholar 

  26. Kang, S. S., Zhou, J., Wong, P.W., Kowalisyn, J., and Strokosch, G. (1988) Intermediate homo-cysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. American Journal of Human Genetics. 43, 414–421.

    CAS  PubMed  Google Scholar 

  27. Haagsma, C. J., Blom, H. J., van Riel, P. L., et al. (1999) Influence of sulphasalazine, meth-otrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 58, 79–84.

    Article  CAS  PubMed  Google Scholar 

  28. van Ede, A. E., Laan, R. F., Blom, H. J., et al. (2001) The C677T mutation in the methylene-tetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients. Arthritis and Rheumatism. 44, 2525–2530.

    Article  PubMed  Google Scholar 

  29. Berkun, Y., Levartovsky, D., Rubinow, A., et al. (2004) Methotrexate related adverse effects in patients with rheumatoid arthritis are associated with the A1298C polymorphism of the MTHFR gene. Annals of the Rheumatic Diseases. 63, 227–231.

    Article  Google Scholar 

  30. Urano, W., Taniguchi, A., Yamanaka, H., et al. (2002) Polymorphisms in the methylenetet-rahydrofolate 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. 12, 183–190.

    Article  CAS  PubMed  Google Scholar 

  31. Horie, N., Aiba, H., Oguro, K., Hojo, H., and Takeishi, K. (1995) Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 5 -terminal regulatory region of the human gene for thymidylate synthase. Cell Structure and Function. 20, 191–197.

    Article  CAS  PubMed  Google Scholar 

  32. Kawakami, K., Omura, K., Kanehira, E., and Watanabe, Y. (1999) Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Research. 19, 3249–52.

    CAS  PubMed  Google Scholar 

  33. DiPaolo, A., and Chu, E. (2004) The role of thymidylate synthase as a molecular biomarker. Clinical Cancer Research. 10, 411–412.

    Article  CAS  PubMed  Google Scholar 

  34. Pullarkat, S. T., Stoehlmacher, J., Ghaderi, V., et al. (2001) Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics Journal. 1, 65–70.

    CAS  PubMed  Google Scholar 

  35. Ulrich, C. M., Bigler, J., Velicer, C. M., Greene, E. A., and Farin, F. M., Potter, J. D. (2000) Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiology, Biomarkers and Prevention. 9, 1381–1385.

    CAS  PubMed  Google Scholar 

  36. Grzybowska, E. A., Wilczynska, A., and Siedlecki, J. A. (2001) Regulatory functions of 3́UTRs. Biochemical and Biophysical Research Communications. 288, 291–295.

    Article  CAS  PubMed  Google Scholar 

  37. Kumagai, K., Hiyama, K., Oyama, T., Maeda, H., and Kohno, N. (2003) Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis. International Journal of Molecular Medicine. 11, 593–600.

    CAS  PubMed  Google Scholar 

  38. Wessels, J. A., de Vries-Bouwstra, J. K., Heijmans, B. T., et al. (2006) Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis and Rheumatism. 54, 1087–1095.

    Article  CAS  PubMed  Google Scholar 

  39. Dervieux, T., Furst, D., Lein, D. O., et al. (2004) 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 and Rheumatism. 50, 2766–2774.

    Article  CAS  PubMed  Google Scholar 

  40. Stolk, J.N., Boerbooms, A. M., de Abreu, R. A., et al. (1998) Reduced thiopurine methyltransferase activity and development of side effects of azathioprine treatment in patients with rheumatoid arthritis. Arthritis and Rheumatism. 41, 1858–1866.

    Article  CAS  PubMed  Google Scholar 

  41. Krynetski, E. Y., Tai, H. L., Yates, C. R., et al. (1996) Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms. Pharmacogenetics. 6, 279–290.

    Article  CAS  PubMed  Google Scholar 

  42. Tai, H. L., Krynetski, E. Y., Yates, C. R., et al. (1996) Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians. American Journal of Human Genetics. 58, 694–702.

    CAS  PubMed  Google Scholar 

  43. Tai, H. L., Krynetski, E. Y., Schuetz, E. G., Yanishevski, Y., and Evans,W. E. (1997) Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT3A, TPMT2): mechanisms for the genetic polymorphism of TPMT activity. Proceedings of the National Academy of Sciences of the United States of America. 94, 6444–6449.

    Article  CAS  PubMed  Google Scholar 

  44. Yates, C. R., Krynetski, E. Y., Loennechen, T., et al. (1997) Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Annals of Internal Medicine. 126, 608–614.

    CAS  PubMed  Google Scholar 

  45. Ameyaw, M. M., Collie-Duguid, E. S., Powrie, R. H., Ofori-Adjei, D., and McLeod, H. L. (1999) Thiopurine methyltransferase alleles in British and Ghanaian populations. Human Molecular Genetics. 8, 367–370.

    Article  CAS  PubMed  Google Scholar 

  46. Hon, Y. Y., Fessing, M. Y., Pui, C. H., Relling, M. V., Krynetski, E. Y., and Evans, W. E. (1998) Polymorphism of the thiopurine S-methyltransferase gene in African-Americans. Human Molecular Genetics. 8, 371–376.

    Article  Google Scholar 

  47. Evans, W. E., Hon, Y. Y., Bomgaars, L., et al. (2001) Preponderance of thiopurine S-methyl-transferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. Journal of Clinical Oncology. 19, 2293–2301.

    CAS  PubMed  Google Scholar 

  48. Black, A. J., McLeod, H. L., Capell, H. A., et al. (1998) Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Annals of Internal Medicine. 129, 716–718.

    CAS  PubMed  Google Scholar 

  49. Corominas, H., Domenech, M., Laiz, A., et al. (2003) Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients? Rheumatology. 42, 40–45.

    Article  CAS  PubMed  Google Scholar 

  50. Kerstens, P. J., Stolk, J. N., De Abreu, R. A., Lambooy, L. H., van de Putte, L. B., and Boerbooms, A. A. (1995) Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis. Arthritis and Rheumatism. 38, 142–145.

    Article  CAS  PubMed  Google Scholar 

  51. Das, K. M., Eastwood, M. A., McManus, J. P., and Sircus, W. (1973) Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. New England Journal of Medicine. 289, 491–495.

    Article  CAS  PubMed  Google Scholar 

  52. Pullar, T., and Capell, H. A. (1986) Variables affecting efficacy and toxicity of sulphasalazine in rheumatoid arthritis. A review. Drugs. 32(suppl. 1), 54–57.

    Article  PubMed  Google Scholar 

  53. Tanaka, E., Taniguchi, A., Urano, W., et al. (2002) Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene. Journal of Rheumatology. 29, 2492–2499.

    CAS  PubMed  Google Scholar 

  54. Wadelius, M., Stjernberg, E., Wiholm, B. E., and Rane, A. (2000) Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis. Pharmacogenetics. 10, 35–41.

    Article  CAS  PubMed  Google Scholar 

  55. Genovese, M. C., Bathon, J. M., Martin, R. W., et al. (2002) Etanercept vs methotrexate in patients with early rheumatoid arthritis: 2-yr radiographic and clinical outcomes. Arthritis and Rheumatism. 46, 1443–1450.

    Article  CAS  PubMed  Google Scholar 

  56. Maini, R. N., Breedveld, F. C., Kalden, J. R., et al. (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis and Rheumatism. 41, 1552–1563.

    Article  CAS  PubMed  Google Scholar 

  57. Keystone, E. C., Kavanaugh, A. F., Sharp, J. T., et al. (2004) Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis and Rheumatism. 50, 1400–1411.

    Article  CAS  PubMed  Google Scholar 

  58. Allen, R. D. (1999) Polymorphism of the human TNF-alpha promoter–random variation or functional diversity? Molecular Immunology. 36, 1017–1027.

    Article  CAS  PubMed  Google Scholar 

  59. Udalova, I. A., Nedospasov, S. A., Webb, G. C., Chaplin, D. D., and Turetskaya, R. L. (1993) Highly informative typing of the human TNF locus using six adjacent polymorphic markers. Genomics. 16, 180–186.

    Article  CAS  PubMed  Google Scholar 

  60. Morita, C., Horiuchi, T., Tsukamoto, H., et al. (2001) Association of tumor necrosis factor receptor type II polymorphism 196R with systemic lupus erythematosus in the Japanese: molecular and functional analysis. Arthritis and Rheumatism. 44, 2819–2827.

    Article  CAS  PubMed  Google Scholar 

  61. Santee, S. M., and Owen-Schaub, L. B. (1996) Human tumor necrosis factor receptor p75/80 (CD120b) gene structure and promoter characterization. Journal of Biological Chemistry. 271, 21151–21159.

    Article  CAS  PubMed  Google Scholar 

  62. Mugnier, B., Balandraud, N., Darque, A., Roudier, C., Roudier, J., and Reviron, D. (2003) Polymorphism at position −308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis. Arthritis and Rheumatism. 48, 1849–1852.

    Article  CAS  PubMed  Google Scholar 

  63. Barrera, P., Joosten, L. A., den Broeder, A. A., van de Putte, L. B., van Riel, P. L., and van den Berg, W. B. (2001) Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFalpha in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 60, 660–669.

    Article  CAS  PubMed  Google Scholar 

  64. Cuchacovich, M., Ferreira, L., Aliste, M., et al. (2004) Tumour necrosis factor-alpha (TNF-alpha) levels and influence of −308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis. Scandinavian Journal of Rheumatology. 33, 228–232.

    Article  CAS  PubMed  Google Scholar 

  65. Fabris, M., Tolusso, B., Di Poi, E., Assaloni, R., Sinigaglia, L., and Ferraccioli, G. (2002) Tumor necrosis factor-alpha receptor II polymorphism in patients from southern Europe with mild-moderate and severe rheumatoid arthritis. Journal of Rheumatology. 29, 1847–1850.

    CAS  PubMed  Google Scholar 

  66. Gregersen, P. K., Silver, J., and Winchester, R.J. (1987) The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis and Rheumatism. 30, 1205–1213.

    Article  CAS  PubMed  Google Scholar 

  67. Waldron-Lynch, F., Adams, C., Amos, C., et al. (2001) Tumour necrosis factor 5 promoter single nucleotide polymorphisms influence susceptibility to rheumatoid arthritis (RA) in immunogenetically defined multiplex RA families. Genes and Immunity. 2, 82–87.

    Article  CAS  PubMed  Google Scholar 

  68. Mulcahy, B., Waldron-Lynch, F., McDermott, M. F., et al. (1996) Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis. American Journal of Human Genetics. 59, 676–683.

    CAS  PubMed  Google Scholar 

  69. Martinez, A., Salido, M., Bonilla, G., et al. (2004) Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients. Arthritis and Rheumatism. 50, 1077–1082.

    Article  CAS  PubMed  Google Scholar 

  70. Criswell, L. A., Lum, R. F., Turner, K. N., et al. (2004) The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis and Rheumatism. 50, 2750–2756.

    Article  CAS  PubMed  Google Scholar 

  71. Ranganathan, P., Culverhouse, R., Marsh, S., et al. (2004) Single nucleotide polymorphism profiling across the methotrexate pathway in normal subjects and patients with rheumatoid arthritis. Pharmacogenomics. 5, 559–569.

    Article  CAS  PubMed  Google Scholar 

  72. Veenstra, D. L., Higashi, M. K., and Phillips, K. A. (2000) Assessing the cost-effectiveness of pharmacogenomics. AAPS pharmSci. 2, E29.

    Article  CAS  PubMed  Google Scholar 

  73. Ranganathan, P., and McLeod, H. L. (2006) Methotrexate pharmacogenetics. Arthritis and Rheumatism. 2006; 54, 1366–1377.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Prabha Ranganathan

Authors
  1. Prabha Ranganathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. PharmTao, Santa Clara, CA, USA

    Qing Yan

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Ranganathan, P. (2008). Pharmacogenomics in Rheumatoid Arthritis. In: Yan, Q. (eds) Pharmacogenomics in Drug Discovery and Development. Methods in Molecular Biology™, vol 448. Humana Press. https://doi.org/10.1007/978-1-59745-205-2_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-205-2_14

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-887-4

  • Online ISBN: 978-1-59745-205-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation