Skip to main content

Advertisement

SpringerLink
Log in

Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

The aim of this study was to determine whether the interleukin-10 (IL-10) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-10 −1082 G/A, −592 C/A, −892 C/T and IL-10.R polymorphisms and RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 16 studies (19 comparisons) involving 2647 RA patients and 3383 controls were considered in the meta-analysis. Meta-analysis of the IL-10 −1082 G/A polymorphism showed no association with RA in the study subjects, or in European or Asian subjects. However, meta-analysis of the −1082 G allele in 4 studies in Hardy–Weinberg equilibrium showed a significant association with RA (OR = 1.217, 95% CI = 1.027–1.442, P = 0.0236). In contrast, meta-analysis of the C allele, the CC genotype, and of the CC versus the AA genotype of the IL-10 −592 C/A polymorphism showed significant associations with RA. The overall ORs of the associations between the C allele and RA were 0.684 and 0.758 (95% CI = 0.494–0.946, P = 0.022; 95% CI = 0.475–1.210, P = 0.045) in all study subjects and Asians. Meta-analysis of the CC + CT versus TT genotype and of the CC versus TT genotype of the IL-10 −892 C/T polymorphism revealed significant associations with RA. The overall OR of the association between the C allele carrier and RA was 0.552 (95% CI = 0.375–0.812, P = 0.003). No association was found between the IL10.R2 alleles and RA. This meta-analysis suggests that the IL-10 −592 C/A polymorphism confers susceptibility to RA in Asians and that the IL-10 −1082 G/A and −892 C/T polymorphisms are associated with RA susceptibility. These findings suggest the IL-10 genes confer susceptibility to RA.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Harris ED Jr (1990) Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med 322:1277–1289

    Article  PubMed  Google Scholar 

  2. Deighton CM, Walker DJ, Griffiths ID, Roberts DF (1989) The contribution of HLA to rheumatoid arthritis. Clin Genet 36:178–182

    Article  PubMed  CAS  Google Scholar 

  3. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    Article  PubMed  CAS  Google Scholar 

  4. Taga K, Tosato G (1992) IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 148:1143–1148

    PubMed  CAS  Google Scholar 

  5. Eskdale J, Wordsworth P, Bowman S, Field M, Gallagher G (1997) Association between polymorphisms at the human IL-10 locus and systemic lupus erythematosus. Tissue Antigens 49:635–639

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Guzowski D, Chandrasekaran A, Gawel C, Palma J, Koenig J, Wang XP, Dosik M, Kaplan M, Chu CC, Chavan S, Furie R, Albesiano E, Chiorazzi N, Goodwin L (2005) Analysis of single nucleotide polymorphisms in the promoter region of interleukin-10 by denaturing high-performance liquid chromatography. J Biomol Tech 16:154–166

    PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Paradowska-Gorycka A, Trefler J, Maciejewska-Stelmach J, Lacki JK (2010) Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patients. Int J Immunogenet 37:225–231

    Article  PubMed  CAS  Google Scholar 

  10. Ying B, Shi Y, Pan X, Song X, Huang Z, Niu Q, Cai B, Wang L (2011) Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. Mol Biol Rep 38:379–385

    Article  PubMed  CAS  Google Scholar 

  11. de Paz B, Alperi-Lopez M, Ballina-Garcia FJ, Prado C, Mozo L, Gutierrez C, Suarez A (2010) Interleukin 10 and tumor necrosis factor-alpha genotypes in rheumatoid arthritis—association with clinical response to glucocorticoids. J Rheumatol 37:503–511

    Article  PubMed  Google Scholar 

  12. Menegatti E, Davit A, Francica S, Berardi D, Rossi D, Baldovino S, Tovo PA, Sena LM, Roccatello D (2009) Genetic factors associated with rheumatoid arthritis and systemic vasculitis: evaluation of a panel of polymorphisms. Dis Markers 27:217–223

    PubMed  CAS  Google Scholar 

  13. Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S (2010) Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 30:1211–1217

    Article  PubMed  CAS  Google Scholar 

  14. Trajkov D, Mishevska-Perchinkova S, Karadzova-Stojanoska A, Petlichkovski A, Strezova A, Spiroski M (2009) Association of 22 cytokine gene polymorphisms with rheumatoid arthritis in population of ethnic Macedonians. Clin Rheumatol 28:1291–1300

    Article  PubMed  Google Scholar 

  15. Ates O, Hatemi G, Hamuryudan V, Topal-Sarikaya A (2008) Tumor necrosis factor-alpha and interleukin-10 gene promoter polymorphisms in Turkish rheumatoid arthritis patients. Clin Rheumatol 27:1243–1248

    Article  PubMed  Google Scholar 

  16. Hee CS, Gun SC, Naidu R, Gupta E, Somnath SD, Radhakrishnan AK (2007) Comparison of single nucleotide polymorphisms in the human interleukin-10 gene promoter between rheumatoid arthritis patients and normal subjects in Malaysia. Mod Rheumatol 17:429–435

    Article  PubMed  CAS  Google Scholar 

  17. Moreno OM, Gonzalez CI, Saaibi DL, Otero W, Badillo R, Martin J, Ramirez G (2007) Polymorphisms of IL-10 gene promoter and rheumatoid arthritis in a Colombian population. Biomedica 27:56–65

    PubMed  Google Scholar 

  18. Pawlik A, Kurzawski M, Szklarz BG, Herczynska M, Drozdzik M (2005) Interleukin-10 promoter polymorphism in patients with rheumatoid arthritis. Clin Rheumatol 24:480–484

    Article  PubMed  Google Scholar 

  19. Padyukov L, Hytonen AM, Smolnikova M, Hahn-Zoric M, Nilsson N, Hanson LA, Tarkowski A, Klareskog L (2004) Polymorphism in promoter region of IL10 gene is associated with rheumatoid arthritis in women. J Rheumatol 31:422–425

    PubMed  CAS  Google Scholar 

  20. Martinez A, Pascual M, Pascual-Salcedo D, Balsa A, Martin J, de la Concha EG (2003) Genetic polymorphisms in Spanish rheumatoid arthritis patients: an association and linkage study. ***Genes Immun 4:117–121

    Article  PubMed  CAS  Google Scholar 

  21. MacKay K, Milicic A, Lee D, Tikly M, Laval S, Shatford J, Wordsworth P (2003) Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse populations. Rheumatology (Oxford) 42:149–153

    Article  CAS  Google Scholar 

  22. Cantagrel A, Navaux F, Loubet-Lescoulie P, Nourhashemi F, Enault G, Abbal M, Constantin A, Laroche M, Mazieres B (1999) Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis Rheum 42:1093–1100

    Article  PubMed  CAS  Google Scholar 

  23. Eskdale J, McNicholl J, Wordsworth P, Jonas B, Huizinga T, Field M, Gallagher G (1998) Interleukin-10 microsatellite polymorphisms and IL-10 locus alleles in rheumatoid arthritis susceptibility. Lancet 352:1282–1283

    Article  PubMed  CAS  Google Scholar 

  24. Coakley G, Mok CC, Hajeer AH, Ollier WE, Turner D, Sinnott PJ, Hutchinson IV, Panayi GS, Lanchbury JS (1998) Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty’s syndrome. Br J Rheumatol 37:988–991

    Article  PubMed  CAS  Google Scholar 

  25. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK, Harley JB (2007) The PTPN22 C1858T functional polymorphism and autoimmune diseases–a meta-analysis. Rheumatology (Oxford) 46:49–56

    Article  CAS  Google Scholar 

  26. Nath SK, Harley JB, Lee YH (2005) Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet 118:225–234

    Article  PubMed  CAS  Google Scholar 

  27. Lee YH, Witte T, Momot T, Schmidt RE, Kaufman KM, Harley JB, Sestak AL (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52:3966–3974

    Article  PubMed  CAS  Google Scholar 

  28. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  29. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  30. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315:1533–1537

    Article  PubMed  CAS  Google Scholar 

  31. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  32. Huizinga TW, Keijsers V, Yanni G, Hall M, Ramage W, Lanchbury J, Pitzalis C, Drossaers-Bakker WK, Westendorp RG, Breedveld FC, Panayi G, Verweij CL (2000) Are differences in interleukin 10 production associated with joint damage? Rheumatology (Oxford) 39:1180–1188

    Article  CAS  Google Scholar 

  33. Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA, Maillere B, Kay AB, Larche M (2006) Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy 36:465–474

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (grant no. A084794).

Conflict of interest

The authors have no financial or non-financial conflict of interest to declare.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5 ga, Seongbuk-gu, Seoul, 136-705, Korea

    Young Ho Lee, Sung Jae Choi, Jong Dae Ji & Gwan Gyu Song

  2. Division of Rheumatology, Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul, Korea

    Sang-Cheol Bae

Authors
  1. Young Ho Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sang-Cheol Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sung Jae Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jong Dae Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gwan Gyu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, Y.H., Bae, SC., Choi, S.J. et al. Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Mol Biol Rep 39, 81–87 (2012). https://doi.org/10.1007/s11033-011-0712-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-0712-7

Keywords

Search

Navigation