Publish in this journal
Journal Information
Vol. 5. Issue 6.
Pages 268-279 (November - December 2009)
Download PDF
More article options
Vol. 5. Issue 6.
Pages 268-279 (November - December 2009)
DOI: 10.1016/S2173-5743(09)70135-2
Full text access
Gene polymorphisms and pharmacogenetics in rheumatoid arthritis
Polimorfismos genéticos y farmacogenética en la artritis reumatoide
Ignacio Rego-Pérez, Mercedes Fernández-Moreno, Vanessa Carreira-García, Francisco J. Blanco??
Corresponding author

Corresponding author.
Unidad de Investigación del Envejecimiento Osteoarticular, Laboratorio de Investigación, INIBIC, División de Reumatología, A Coruña, Spain
Article information

Rheumatoid arthritis (RA) is a systemic, chronic, and inflammatory disease of unknown aetiology with a genetic predisposition. The advent of new biological agents, as well as the more traditional diseasemodifying anti rheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response regarding disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient's genetic profile.

Chronic and severe forms of gout are frequently wrongly evaluated from the clinical standpoint.

Rheumatoid arthritis
Tumor necrosis factor
Gene polymorphisms

La artritis reumatoide (AR) es una enfermedad inflamatoria, sistémica y crónica de etiología desconocida y con predisposición genética. La llegada de los nuevos agentes biológicos, así como los ya conocidos fármacos antirreumáticos modificadores de la enfermedad, condujeron a una eficacia elevada en los tratamientos de la AR. Sin embargo, no todos los sujetos muestran el mismo grado de progresión de la enfermedad como respuesta a estos tratamientos. Estas variaciones demuestran que los sujetos con AR deben tener diferentes mecanismos de regulación génica. Los polimorfismos detectados en las regiones reguladoras no codificantes del sistema inmune y las variaciones genéticas de las enzimas que metabolizan los fármacos demuestran que este tipo de variaciones tiene una importancia funcional y evolutiva elevada, lo que proporciona nuevas pistas para el desarrollo de nuevas estrategias terapéuticas. La farmacogenética es un campo que avanza rápidamente y promete el desarrollo de tratamientos adaptados al perfil genético del sujeto en un futuro cercano.

Palabras clave:
Artritis reumatoide
Factor de necrosis tumoral
Polimorfismos genéticos
Full text is only aviable in PDF
W.E. Evans, M.V. Relling.
Pharmacogenomics: Translating functional genomics into rational therapeutics.
Science, 286 (1999), pp. 487-491
A.J. Silman, A.J. MacGregor, W. Thomson, S. Holligan, D. Carthy, A. Farhan, et al.
Twin concordance rates for rheumatoid arthritis: Results from a nationwide study.
Br J Rheumatol, 32 (1993), pp. 903-907
F. Cornelis, S. Fauré, M. Martínez.
Rheumatoid arthritis genome scan and pretative autoimmunity locus.
Arthritis Reum, 40 (1997), pp. S329
M. Pierik, P. Rutgeerts, R. Vlietinck, S. Vermeire.
Pharmacogenetics in inflammatory bowel disease.
World J Gastroenterol, 12 (2006), pp. 3657-3667
G.T. Nepom.
Major histocompatibility complex-directed susceptibility to rheumatoid arthritis.
Adv Immunol, 68 (1998), pp. 315-332
M. Feldmann, F.M. Brennan, R.N. Maini.
Role of cytokines in rheumatoid arthritis.
Annu Rev Immunol, 14 (1996), pp. 397-440
C.M. Deighton, D.J. Walker, I.D. Griffiths, D.F. Roberts.
The contribution of HLA to rheumatoid arthritis.
Clin Genet, 36 (1989), pp. 178-182
P.K. Gregersen, J. Silver, R.J. Winchester.
The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis.
Arthritis Rheum, 30 (1987), pp. 1205-1213
A. McGregor, W. Ollier, W. Thomson, D. Jawaheer, A. Silman.
HLA-DRB1 *0401/0404 genotype and rheumatoid arthritis: Increased association in men, young age at onset, and disease severity.
J Rheumatol, 22 (1995), pp. 1032-1036
J.D. Reveille.
Genetic studies in the rheumatic diseases: Present status and implications for the future.
J Rheumatol, 72 (2005), pp. 10-13
A. Martínez, M. Salido, G. Bonilla, D. Pascual-Salcedo, M. Fernández-Arquero, S. de Miguel, et al.
Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients.
Arthritis Rheum, 50 (2004), pp. 1077-1082
L. Padyukov, J. Lampa, M. Heimburger, S. Ernestam, T. Cederholm, I. Lundkvist, et al.
Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis.
Ann Rheum Dis, 62 (2003), pp. 526-529
F.M. Brennan, R.N. Maini, M. Feldmann.
TNF alpha -a pivotal role in rheumatoid arthritis?.
Br J Rheumatol, 31 (1992), pp. 293-298
C.A. Smith, T. Farrah, R.G. Goodwin.
The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death.
Cell, 76 (1994), pp. 959-962
P. Vassalli.
The pathophysiology of tumor necrosis factors.
Annu Rev Immunol, 10 (1992), pp. 411-452
C.L. Verweij.
Tumour necrosis factor gene polymorphisms as severity markers in rheumatoid arthritis.
Ann Rheum Dis, 58 (1999), pp. I20-I26
R.D. Campbell, J. Trowsdale.
Map of the human MHC.
Immunol Today, 14 (1993), pp. 349-352
A.G. Wilson, N. de Vries, F. Pociot, F.S. Di Giovine, L.B. Van der Putte, G.W. Duff.
An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles.
J Exp Med, 177 (1993), pp. 557-560
C.O. Jacob, Z. Fronek, G.D. Lewis, M. Koo, J.A. Hansen, H.O. McDevitt.
Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: Relevance to genetic predisposition to systemic lupus erythematosus.
Proc Natl Acad Sci USA, 87 (1990), pp. 1233-1237
B.M. Brinkman, T.W. Huizinga, S.S. Kurban, E.A. van der Velde, G.M. Schreuder, J.M. Hazes, et al.
Tumor necrosis factor alpha gene polymorphisms in rheumatoid arthritis: Association with susceptibility to, or severity of disease?.
Br J Rheumatol, 36 (1997), pp. 516-521
I.A. Udalova, A. Richardson, A. Denys, C. Smith, H. Ackerman, B. Foxwell, et al.
Functional consequences of a polymorphism affecting NF-kappaB p50-p50 binding to the TNF promoter region.
Mol Cell Biol, 20 (2000), pp. 9113-9119
J. Newton, M.A. Brown, A. Milicic, H. Ackerman, C. Darke, J.N. Wilson, et al.
The effect of HLA-DR on susceptibility to rheumatoid arthritis is influenced by the associated lymphotoxin alpha-tumor necrosis factor haplotype.
Arthritis Rheum, 48 (2003), pp. 90-96
N.W. Kuo, P.A. Lympany, V. Menezo, A.L. Lagan, S. John, T.K. Yeo, et al.
TNF-857T, a genetic risk marker for acute anterior uveitis.
Invest Opthalmol Vis Sci, 46 (2005), pp. 1565-1571
A. Akman, N. Sallakci, M. Coskun, A. Bacanli, U. Yavuzer, E. Alpsoy, et al.
TNF-alpha gene 1031 T/C polymorphism in Turkish patients with Behcet's disease.
Br J Dermatol, 155 (2006), pp. 350-356
A. Smerdel, B.A. Lie, R. Ploski, B.P. Koeleman, O. Forre, E. Thorsby, et al.
A gene in the telomeric HLA complex distinct from HLA-A is involved in predisposition to juvenile idiopathic arthritis.
Arthritis Rheum, 46 (2002), pp. 1614-1619
S.M. Santee, L.B. Owen-Schaub.
Human tumor necrosis factor receptor p75/80 (CD120b) gene structure and promoter characterization.
J Biol Chem, 271 (1996), pp. 21151-21159
P. Ranganathan.
Pharmacogenetics of tumor necrosis factor antagonists in rheumatoid arthritis.
Pharmacogenomics, 6 (2005), pp. 481-490
I.A. Udalova, S.A. Nedospasov, G.C. Webb, D.D. Chaplin, R.L. Turetskaya.
Highly informative typing of the human TNF locus using six adjacent polymorphic markers.
Genomics, 16 (1993), pp. 180-186
B. Mulcahy, F. Waldron-Lynch, M.F. McDermott, C. Adams, C.I. Amos, D.K. Zhu, et al.
Genetic variability in the tumor necrosis factor-lymphotoxin region influences susceptibility to rheumatoid arthritis.
Am J Hum Genet, 59 (1996), pp. 676-683
W.B. van den Berg.
Arguments for interleukin 1 as a target in chronic arthritis.
Ann Rheum Dis, 59 (2000), pp. I81-I84
M.J. Nicklin, A. Weith, G.W. Duff.
A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes.
Genomics, 19 (1994), pp. 382-384
A. Cox, N.J. Camp, M.J. Nicklin, F.S. Di Giovine, G.W. Duff.
An analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a novel grouping method for multiallelic markers.
Am J Hum Genet, 62 (1998), pp. 1180-1188
T.L. McDowell, J.A. Symons, R. Ploski, O. Forre, G.W. Duff.
A genetic association between juvenile rheumatoid arthritis and a novel interleukin-1 alpha polymorphism.
Arthritis Rheum, 38 (1995), pp. 221-228
P.A. van den Velden, P.H. Reitsma.
Amino acid dimorphism in IL1A is detectable by PCR amplification.
Hum Mol Genet, 2 (1993), pp. 1753
F.S. Di Giovine, E. Takhsh, A.I. Blakemore, G.W. Duff.
Single base polymorphism at -511 in the human interleukin-1 beta gene (IL1 beta).
Hum Mol Genet, 1 (1992), pp. 450
F. Pociot, J. Molvig, L. Wogensen, H. Worsaae, J. Nerup.
A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro.
Eur J Clin Invest, 22 (1992), pp. 396-402
F.S. Di Giovine, N.J. Camp, A. Cox.
Detection and population analysis of IL-1 and TNF gene polymorphisms.
Cytokine Molecular Biology, pp. 21-46
A. Cantagrel, F. Navaux, P. Loubet-Lescoulie, F. Nourhashemi, G. Enault, M. Abbal, et al.
Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: Relationship to occurrence and severity of rheumatoid arthritis.
N. Buchs, F.S. Di Giovine, T. Silvestre, E. Vannier, G.W. Duff, P. Miossec.
IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: Interaction with their plasma levels.
Genes Immun, 2 (2001), pp. 222-228
S. Santtila, K. Savinainen, M. Hurme.
Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro.
Scand J Immunol, 47 (1998), pp. 195-198
J. Hulkkonen, P. Laippala, M. Hurme.
A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1 beta plasma levels in healthy individuals.
Eur Cytokine Netw, 11 (2000), pp. 251-255
R. Dominici, M. Cattaneo, G. Malferrari, D. Archi, C. Mariani, L.M. Grimaldi, et al.
Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region of interleukin-2 alpha.
Immunogenetics, 54 (2002), pp. 82-86
M. Whyte, R. Hubbard, R. Meliconi, M. Whidborne, V. Eaton, C. Bingle, et al.
Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms.
Am J Respir Crit Care Med, 162 (2000), pp. 755-758
M. Feldmann, F.M. Brennan, B.M. Foxwell, R.N. Maini.
The role of TNF alpha and IL-1 in rheumatoid arthritis.
Curr Dir Autoimmun, 3 (2001), pp. 188-199
J. Uson, A. Balsa, D. Pascual-Salcedo, J.A. Cabezas, J.M. González-Tarrio, E. Martín-Mola, et al.
Soluble interleukin 6 (IL-6) receptor and IL-6 levels in serum and synovial fluid of patients with different arthropathies.
J Rheumatol, 24 (1997), pp. 2069-2075
Z. Xing, J. Gauldie, G. Cox, H. Baumann, M. Jordana, X.F. Lei, et al.
IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.
J Clin Invest, 101 (1998), pp. 311-320
H. Tilg, E. Trehu, M.B. Atkins, C.A. Dinarello, J.W. Mier.
Interleukin-6 (IL-6) as an antiinflammatory cytokine: Induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55.
Blood, 83 (1994), pp. 113-118
M. Pascual, A. Nieto, L. Mataran, A. Balsa, D. Pascual-Salcedo, J. Martín.
IL-6 promoter polymorphisms in rheumatoid arthritis.
Genes Immun, 1 (2000), pp. 338-340
D. Fishman, G. Faulds, R. Jeffery, V. Mohamed-Ali, J.S. Yudkin, S. Humphries, et al.
The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.
J Clin Invest, 102 (1998), pp. 1369-1376
A. Martínez, M. Pascual, D. Pascual-Salcedo, A. Balsa, J. Martín, E.G. de la Concha.
Genetic polymorphisms in Spanish rheumatoid arthritis patients: An association and linkage study.
Genes Immun, 4 (2003), pp. 117-121
A.E. Chernoff, E.V. Granowitz, L. Shapiro, E. Vannier, G. Lonnemann, J.B. Angel, et al.
A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses.
J Immunol, 154 (1995), pp. 5492-5499
D.M. Turner, D.M. Williams, D. Sankaran, M. Lazarus, P.J. Sinnott, I.V. Hutchinson.
An investigation of polymorphism in the interleukin-10 gene promoter.
Eur J Immunogenet, 24 (1997), pp. 1-8
N. Braun, U. Michel, B.P. Ernst, R. Metzner, A. Bitsch, F. Weber, et al.
Gene polymorphism at position -308 of the tumor-necrosis-factor-alpha (TNF- alpha) in multiple sclerosis and its influence on the regulation of TNF-alpha production.
Neurosci Lett, 215 (1996), pp. 75-78
L. Padyukov, A.M. Hytonen, M. Smolnikova, M. Hahn-Zoric, N. Nilsson, L.A. Hanson, et al.
Polymorphism in promoter region of IL-10 gene is associated with rheumatoid arthritis in women.
J Rheumatol, 31 (2004), pp. 422-425
P. Ranganathan, H.L. McLeod.
Methotrexate pharmacogenetics: The first step toward individualized therapy in rheumatoid arthritis.
Arthritis Rheum, 54 (2006), pp. 1366-1377
T. Dervieux, D.O. Lein, G. Park, R. Barham, K. Smith, M. Walsh.
Single nucleotide polymorphisms (SNPs) in the folate/purine synthesis pathway predict methotrexate0s effect in rheumatoid arthritis.
Arthritis Reum, 48 (2003), pp. S438
A. Pawlik, J. Wrzesniewska, I. Fiedorowicz-Fabrycy, B. Gawronska-Szklarz.
The MDR1 3435 polymorphism in patients with rheumatoid arthritis.
Int J Clin Pharmacol Ther, 42 (2004), pp. 496-503
S.S. Kang, J. Zhou, P.W. Wong, J. Kowalisyn, G. Strokosch.
Intermediate homocysteinemia: A thermolabile variant of methylenetetrahydrofolate reductasa.
Am J Hum Genet, 43 (1988), pp. 414-421
C.J. Haagsma, H.J. Blom, P.L. van Riel, M.A. Vanot Hof, B.A. Giesendorf, D. Van Oppenraaij-Emmerzaal, et al.
Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis.
Ann Rheum Dis, 58 (1999), pp. 79-84
W. Urano, A. Taniguchi, H. Yamanaka, E. Tanaka, H. Nakajima, Y. Matsuda, et al.
Polymorphisms in the methylenetetrahydrofolate reductasa 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 (2002), pp. 183-190
A. Taniguchi, W. Urano, E. Tanaka, S. Furihata, S. Kamitsuji, E. Inoue, et al.
Validation of the associations between single nucleotide polymorphisms or haplotypes and responses to disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A proposal for prospective pharmacogenomic study in clinical practice.
Pharmacogenet Genom, 17 (2007), pp. 383-390
T. Dervieux, N. Greenstein, J. Kremer.
Pharmacogenetic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis.
Arthritis Rheum, 54 (2006), pp. 3095-3103
D.L. Berkun, A. Rubinow, H. Orbach, S. Aamar, T. Grenader, I. Abou Atta, et al.
Methotrexate related adverse effects in patients with rheumatoid artritis are associated with the A1298C polymorphism of the MTHFR gene.
Ann Rheum Dis, 63 (2004), pp. 1227-1231
K. Kumagai, K. Hiyama, T. Oyama, H. Maeda, N. Cono.
Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductasa genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis.
Intl J Mol Med, 11 (2003), pp. 593-600
K.R. Herrlinger, J.R. Cummings, M.C. Barnardo, M. Schaw, T. Ahmad, D.P. Jewell.
The pharmacogenetics of methotrexate in inflammatory bowel disease.
Pharma- cogenet Genom, 15 (2005), pp. 705-711
J.A.M. Wessels, S.M. Van der Kooij, S. Le Cessie, W. Kievit, P. Barerra, T.W.J. Allaart, et al.
A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis.
Arthritis Rheum, 56 (2007), pp. 1765-1775
N. Horie, H. Aiba, K. Oguro, H. Hojo, K. Takeishi.
Functional analysis and DNA polymorphism of the tandemly repeated sequences in the 50-terminal regulatory region of the human gene for thymidylate synthase.
Cell Struct Funct, 20 (1995), pp. 191-197
A. DiPaolo, E. Chu.
The role of thymidylate synthase as a molecular biomarker.
Clin Cancer Res, 10 (2004), pp. 411-412
C.M. Ulrich, J. Bigler, C.M. Velicer, E.A. Greene, F.M. Farin, J.D. Potter.
Searching expressed sequence tag databases: Discovery and confirmation of a common polymorphism in the thymidylate synthase gene.
Cancer Epidemiol Biomarkers Prev, 9 (2000), pp. 1381-1385
E.A. Grzybowska, A. Wilczynska, J.A. Siedlecki.
Regulatory functions of 3UTRs.
Biochem Biophys Res Commun, 288 (2001), pp. 291-295
T. Dervieux, D. Furst, D.O. Lein, R. Capps, K. Smith, M. Walsh, 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, 50 (2004), pp. 2766-2774
C.P. Rains, S. Noble, D. Faulds.
Sulfasalazine. A review of its pharmacological properties and therapeutic efficacy in the treatment of rheumatoid arthritis.
Drugs, 50 (1995), pp. 137-156
T. Pullar, H.A. Capell.
Variables affecting efficacy and toxicity of sulphasalazine in rheumatoid arthritis. A review.
Drugs, 32 (1986), pp. 54-57
M. Wadelius, E. Stjernberg, B.E. Wiholm, A. Rane.
Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis.
Pharmacogenetics, 10 (2000), pp. 35-41
E. Tanaka, A. Taniguchi, W. Urano, H. Nakajima, Y. Matsuda, Y. Kitamura, et al.
Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene.
J Rheumatol, 29 (2002), pp. 2492-2499
P. Ranganathan.
Pharmacogenetics of therapies in rheumatoid arthritis.
Drugs today, 41 (2005), pp. 799-814
E.Y. Krynetski, H.L. Tai, C.R. Yates, M.Y. Fessing, T. Loennechen, J.D. Schuetz, et al.
Genetic polymorphism of thiopurine S-methyltransferase: Clinical importance and molecular mechanisms.
Pharmacogenetics, 6 (1996), pp. 279-290
H.L. Tai, E.Y. Krynetsky, E.G. Schuetz, Y. Yanishevsky, W.E. Evans.
Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) ancoded by mutant alleles in humans (TPMT*3A, TPMT*2): Mechanisms for the genetic polymorphism of TPMT activity.
Proc Natl Acad Sci USA, 94 (1997), pp. 6444-6449
H. Corominas, M. Domenech, A. Laiz, I. Vich, C. Geli, C. Diaz, et al.
Is thiopurine methyltransferase genetic polymorphism a major factor for with drawal of azathioprine in rheumatoid arthritis patients?.
Rheumatology, 42 (2003), pp. 40-45
M.C. Genovese, J.M. Bathon, R.W. Martin, R.M. Fleischmann, J.R. Tesser, M.H. Schiff, et al.
Etanercept versus methotrexate in patients with early rheumatoid arthritis: Two-year radiographic and clinical outcomes.
Arthritis Rheum, 46 (2002), pp. 1443-1450
E.C. Keystone, A.F. Kavanaugh, J.T. Sharp, H. Tannenbaum, Y. Hua, L.S. Teoh, et al.
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 Rheum, 50 (2004), pp. 1400-1411
J.D. Greenberg, H. Ostrer.
The promise of pharmacogenetics to TNF antagonists in rheumatoid arthritis.
Bulletin of the NYU Hospital for Joint Diseases, 65 (2007), pp. 139-142
G. Ferraccioli.
The possible clinical application of pharmacogenetics in rheumatology.
J Rheumatol, 30 (2003), pp. 2517-2520
P.E. Lipsky, D.M. van der Heijde, E.W. St Clair, D.E. Furst, F.C. Breedveld, J.R. Kalden, Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group, et al.
Infliximab and methotrexate in the treatment of rheumatoid arthritis.
N Engl J Med, 343 (2000), pp. 1594-1602
G. Bouma, J.B. Crusius, M. Oudkerk Pool, J.J. Kolkman, B.M. von Blomberg, P.J. Kostense, et al.
Secretion of tumour necrosis factor alpha and lymphotoxin alpha in relation to polymorphisms in the TNF genes and HLA-DR alleles. Relevance for inflammatory bowel disease.
Scand J Immunol, 43 (1996), pp. 456-463
M.F. Callan.
Epstein-Barr virus, arthritis, and the development of lymphoma in arthritis patients.
Curr Opin Rheumatol, 16 (2004), pp. 399-405
N. Mohan, E.T. Edwards, T.R. Cupps, P.J. Oliverio, G. Sandberg, H. Crayton, et al.
Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides.
Arthritis Rheum, 44 (2001), pp. 2862-2869
E. Baecklund, A. Ekbom, P. Sparen, N. Feltelius, L. Klareskog.
Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study.
BMJ, 317 (1998), pp. 180-181
P. Emery, L.B.A. van de Putte, P.L.C.M. van Riel, R. Rau, M. Schattenkirchner, G.R. Burmester.
Changes in Pro-MMP-1 in relation to standard measures of disease activity over a 6-month treatment period with adalimumab (D2E7) in rheumatoid arthritis.
Arthritis Reum, 44 (2001), pp. 215
B. Bresnihan, J.M. Álvaro-Gracía, M. Cobby, M. Doherty, Z. Domljan, P. Emery, et al.
Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.
S. Cohen, E. Hurd, J. Cush, M. Schiff, M.E. Weinblatt, L.W. Moreland, et al.
Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: Results of a twenty-four-week, multicenter, randomized, double-blind, placebo- controlled trial.
Arthritis Rheum, 46 (2002), pp. 614-624
R.M. Fleischmann, J. Schechtman, R. Bennett, M.L. Handel, G.R. Burmester, J. Tesser, et al.
Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial.
Arthritis Rheum, 48 (2003), pp. 927-934
S. Guignard, G. Dien, M. Dougados.
Severe systemic inflammatory response syndrome in a patient with adult onset Still's disease treated with the anti-IL1 drug anakinra: A case report.
Clin Exp Rheumatol, 25 (2007), pp. 758-759
G.D. Kalliolias, S.N. Liossis.
The future of the IL-1 receptor antagonist anakinra: From rheumatoid arthritis to adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis.
Expert Opin Investig Drugs, 17 (2008), pp. 349-359
L.A. Criswell, R.F. Lum, K.N. Turner, B. Woehl, Y. Zhu, J. Wang, et al.
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 Rheum, 50 (2004), pp. 2750-2756
E.C. Walsh, K.A. Mather, S.F. Schaffner, L. Farwell, M.J. Daly, N. Patterson, et al.
An integrated haplotype map of the human major histocompatibility complex.
Am J Hum Genet, 73 (2003), pp. 580-590
C.P. Kang, K.W. Lee, D.H. Yoo, C. Kang, S.C. Bae.
The influence of a polymorphism at position -857 of the tumour necrosis factor alpha gene on clinical response to etanercept therapy in rheumatoid arthritis.
Rheumatology (Oxford), 44 (2005), pp. 547-552
M. Fabris, B. Tolusso, E. Di Pol, R. Assaloni, L. Sinigaglia, G. Ferraccioli.
Tumor necrosis factor-alpha receptor II polymorphism in patients from southern Europe with mild-moderate and severe rheumatoid artritis.
J Rheumatol, 29 (2002), pp. 1847-1850
H. Schotte, B. Schluter, S. Drynda, P. Willeke, N. Tidow, G. Assmann, et al.
Interleukin 10 promoter microsatellite polymorphisms are associated with response to long term treatment with etanercept in patients with rheumatoid arthritis.
Ann Rheum Dis, 64 (2005), pp. 575-581
B. Mugnier, N. Balandraud, A. Darque, C. Roudier, J. Roudier, D. Reviron.
Polymorphism at position -308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis.
Arthritis Rheum, 48 (2003), pp. 1849-1852
M. Cuchacovich, L. Ferreira, M. Aliste, L. Soto, J. Cuenca, A. Cruzat, et al.
Tumor necrosis factor-alpha (TNF-alpha) levels and influence of -308 TNF-alpha promoter polymorphism on the responsiveness to infliximab in patients with rheumatoid arthritis.
Scand J Rheumatol, 33 (2004), pp. 228-232
J.E. Fonseca, T. Carvalho, M. Cruz, P. Nero, M. Sobral, A.F. Mourao, et al.
Polymorphism at position-308 of the tumor necrosis factor alpha gene and rheumatoid arthritis pharmacogenetics.
Ann Rheum Dis, 64 (2005), pp. 793-794
J.A. Pinto, I. Rego, C. Fernández López, M. Freire, J.L. Fernández Sueiro, F.J. Blanco, et al.
Polymorphisms in genes encoding TNF-alpha and HLA-DRB1 are not associated with response to infliximab in patients with rheumatoid arthritis.
J Rheumatol, 35 (2008), pp. 177-178
N.J. Camp, A. Cox, F.S. Di Giovine, D. McCabe, W. Rich, G.W. Duff.
Evidence of a pharmacogenomic response to interleukin-l receptor antagonist in rheumatoid arthritis.
Genes Immun, 6 (2005), pp. 467-471
F.C. Arnett, S.M. Edworthy, D.A. Bloch, D.J. McShane, J.F. Fries, N.S. Cooper, et al.
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
Arthritis Reum, 31 (1998), pp. 315-324
E.H. Choy, G.S. Panayi.
Cytokine pathways and joint inflammation in rheumatoid arthritis.
N Engl J Med, 344 (2001), pp. 907-916
S.L. Bridges Jr..
The genetics of rheumatoid arthritis: Influences on susceptibility, severity, and treatment response.
Curr Rheumatol Rep, 1 (1999), pp. 164-171
W.E. Evans, H.L. McLeod.
Pharmacogenomics-drug disposition, drug targets, and side effects.
N Eng J Med, 348 (2003), pp. 538-549
T. Lequerré, A.C. Gauthier-Jauneau, C. Bansard, C. Derambure, M. Hiron, O. VIttecoq, et al.
Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis.
Arthritis Res Ther, 8 (2006), pp. R105
J.N. Hirschhorn, K. Lohmueller, E. Byrne, K.A. Hirschhorn.
A comprenhensive review of genetic association studies.
Copyright © 2009. Sociedad Española de Reumatología and Colegio Mexicano de Reumatología
Reumatología Clínica (English Edition)

Subscribe to our newsletter

Article options
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.