Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

Genetic polymorphisms in Spanish rheumatoid arthritis patients: an association and linkage study

Genes & Immunity volume 4, pages 117–121 (2003)Cite this article

Abstract

HLA polymorphism accounts only for approximately one-third of the genetic predisposition to rheumatoid arthritis (RA). To investigate the role of other loci in the susceptibility to RA, we have performed an analysis of several polymorphisms in genes of immune-related function: IL-10 −1082, −819, −592 promoter single nucleotide polymorphisms (SNPs), IL-10G and IL-10R microsatellites, IL-6 −622 promoter SNP, FcγRIIIA Val/Phe-158 polymorphism, IL-1 receptor antagonist VNTR, and the IKBL+738 T/C mutation. The analysis has been performed on a case–control study and also on RA trios. IL-10G12 was found to be associated with RA in the case–control study (18% in RA patients vs 9% in controls: P=0.001; pc<0.05). This allele was also more often transmitted than not transmitted (10 vs 5). No other allele in the present study is found to be associated to RA. Our data suggest that most of the loci studied play no major role in the susceptibility to RA, the IL-10 gene being the sole exception.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Martinez A, Fernandez-Arquero M, Balsa A et al. Primary association of a MICA allele with protection against rheumatoid arthritis. Arthritis Rheum 2001; 44: 1261–1265.

    Article  CAS  Google Scholar 

  2. Martinez A, Fernandez-Arquero M, Pascual-Salcedo D et al. Primary association of tumor necrosis factor-region genetic markers with susceptibility to rheumatoid arthritis. Arthritis Rheum 2000; 43: 1366–1370.

    Article  CAS  Google Scholar 

  3. Pascual M, Nieto A, Mataran L, Balsa A, Pascual-Salcedo D, Martin J . IL-6 promoter polymorphisms in rheumatoid arthritis. Genes Immun 2000; 1: 338–340.

    Article  CAS  Google Scholar 

  4. Nieto A, Caliz R, Pascual M, Mataran L, Garcia S, Martin J . Involvement of Fcgamma receptor IIIA genotypes in susceptibility to rheumatoid arthritis. Arthritis Rheum 2000; 43: 735–739.

    Article  CAS  Google Scholar 

  5. Fishman D, Faulds G, Jeffery R 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 1998; 102: 1369–1376.

    Article  CAS  Google Scholar 

  6. Eskdale J, Gallagher G . A polymorphic dinucleotide repeat in the human IL-10 promoter. Immunogenetics 1995; 42: 444–445.

    Article  CAS  Google Scholar 

  7. Eskdale J, Kube D, Gallagher G . A second polymorphic dinucleotide repeat in the 5' flanking region of the human IL10 gene. Immunogenetics 1996; 45: 82–83.

    Article  CAS  Google Scholar 

  8. Eskdale J, Kube D, Tesch H, Gallagher G . Mapping of the human IL10 gene and further characterization of the 5′ flanking sequence. Immunogenetics 1997; 46: 120–128.

    Article  CAS  Google Scholar 

  9. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV . An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8.

    Article  CAS  Google Scholar 

  10. Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RG, Huizinga TW . Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 1998; 95: 9465–9470.

    Article  CAS  Google Scholar 

  11. Cantagrel A, Navaux F, Loubet-Lescoulie P et al. Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis Rheum 1999; 42: 1093–1100.

    Article  CAS  Google Scholar 

  12. Hajeer AH, Lazarus M, Turner D et al. IL-10 gene promoter polymorphisms in rheumatoid arthritis. Scand J Rheumatol 1998; 27: 142–145.

    Article  CAS  Google Scholar 

  13. Eskdale J, McNicholl J, Wordsworth P et al. Interleukin-10 microsatellite polymorphisms and IL-10 locus alleles in rheumatoid arthritis susceptibility. Lancet 1998; 352: 1282–1283.

    Article  CAS  Google Scholar 

  14. Arend WP, Malyak M, Guthridge CJ, Gabay C . Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 1998; 16: 27–55.

    Article  CAS  Google Scholar 

  15. Tarlow JK, Blakemore AI, Lennard A et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Hum Genet 1993; 91: 403–404.

    Article  CAS  Google Scholar 

  16. Allcock RJ, Christiansen FT, Price P . The central MHC gene IKBL carries a structural polymorphism that is associated with HLA-A3,B7,DR15. Immunogenetics 1999; 49: 660–665.

    Article  CAS  Google Scholar 

  17. de la Concha EG, Fernandez-Arquero M, Lopez-Nava G et al. Susceptibility to severe ulcerative colitis is associated with polymorphism in the central MHC gene IKBL. Gastroenterology 2000; 119: 1491–1495.

    Article  CAS  Google Scholar 

  18. Salmon JE, Pricop L . Human receptors for immunoglobulin G: key elements in the pathogenesis of rheumatic disease. Arthritis Rheum 2001; 44: 739–750.

    Article  CAS  Google Scholar 

  19. Ravetch JV, Bolland S . IgG Fc receptors. Annu Rev Immunol 2001; 19: 275–290.

    Article  CAS  Google Scholar 

  20. Morgan AW, Griffiths B, Ponchel F et al. Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups. Arthritis Rheum 2000; 43: 2328–2334.

    Article  CAS  Google Scholar 

  21. Nieto A, Pascual M, Caliz R, Mataran L, Martin J . Association of Fc? receptor IIIA polymorphism with rheumatoid arthritis: comment on the article by Morgan et al. Arthritis Rheum 2002; 46: 556–557.

    Article  Google Scholar 

  22. Gibson AW, Edberg JC, Wu J, Westendorp RG, Huizinga TW, Kimberly RP . Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 2001; 166: 3915–3922.

    Article  CAS  Google Scholar 

  23. Kube D, Rieth H, Eskdale J, Kremsner PG, Gallagher G . Structural characterisation of the distal 5′ flanking region of the human interleukin-10 gene. Genes Immun 2001; 2: 181–190.

    Article  CAS  Google Scholar 

  24. D'Alfonso S, Rampi M, Rolando V, Giordano M, Momigliano-Richiardi P . New polymorphisms in the IL-10 promoter region. Genes Immun 2000; 1: 231–233.

    Article  CAS  Google Scholar 

  25. Mullighan CG, Marshall SE, Bunce M, Welsh KI . Variation in immunoregulatory genes determines the clinical phenotype of common variable immunodeficiency. Genes Immun 1999; 1: 137–148.

    Article  CAS  Google Scholar 

  26. Cavet J, Middleton PG, Segall M, Noreen H, Davies SM, Dickinson AM . Recipient tumor necrosis factor-alpha and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus- host disease severity in HLA-matched sibling bone marrow transplants. Blood 1999; 94: 3941–3946.

    CAS  Google Scholar 

  27. Mansfield JC, Holden H, Tarlow JK et al. Novel genetic association between ulcerative colitis and the anti- inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology 1994; 106: 637–642.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Servicio de Inmunología Clínica, Hospital Universitario San Carlos, Madrid, Spain

    A Martinez & E G de la Concha

  2. Instituto de Parasitología y Biomedicina ‘López Neyra’ (CSIC), Granada, Spain

    M Pascual & J Martin

  3. Hospital Universitario La Paz, Madrid, Spain

    D Pascual-Salcedo & A Balsa

Authors
  1. A Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Pascual
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Pascual-Salcedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Balsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E G de la Concha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Martinez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martinez, A., Pascual, M., Pascual-Salcedo, D. et al. Genetic polymorphisms in Spanish rheumatoid arthritis patients: an association and linkage study. Genes Immun 4, 117–121 (2003). https://doi.org/10.1038/sj.gene.6363931

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363931

Keywords

This article is cited by

Search

Advanced search

Quick links