Skip to main content
Log in

Interleukin-6, interleukin-1 gene cluster and interleukin-1 receptor polymorphisms in Iranian patients with juvenile systemic lupus erythematosus

  • Research Article
  • Published:
European Cytokine Network

Abstract

Background

Juvenile systemic lupus erythematosus (JSLE) is a polygenic, autoimmune disorder of unknown origin. As proinflammatory cytokines, including interleukin-6 (IL-6) and the interleukin-1 (IL-1) family, seem to contribute to the pathogenesis of JSLE, this investigation was performed to assess the associations of particular single nucleotide polymorphisms (SNPs) of IL-6 and IL-1 genes in a case-control study.

Methods

Fifty nine JSLE cases were recruited for this study as the patient group, and were compared against 140 healthy, unrelated, control subjects. Using the polymerase chain reaction with the sequence-specific primer method, genotyping was carried out for the IL-6 gene at positions −174 and nt565, as well as the IL-1α gene at position −889, the IL-1β gene at positions −511 and +3962, the interleukin-1 receptor (IL-1R) gene at position Pst-I 1970, and the interleukin-1 receptor antagonist (IL-1Ra) gene at position Mspa-I 11100.

Results

Results of the analyzed data revealed a remarkable, positive association for the promoter sequence of the IL-1β gene at position −511 for T/T in the patient group compared with healthy controls (P value, 0.03). Furthermore, a significant negative association was found between the T/C genotype at the same position on the IL-1β gene in juvenile SLE (P value, 0.03).

Conclusions

cytokine gene polymorphisms might play a role in the pathophysiology of JSLE. Particular IL-1 gene variants could affect individual susceptibility to JSLE.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yap DYH, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus-from bench to bedside. Nephrology 2013; 18: 243.

    Article  CAS  PubMed  Google Scholar 

  2. Tsao BP. Update on human systemic lupus erythematosus genetics. Curr Opin Rheumatol 2004; 16: 513.

    Article  CAS  PubMed  Google Scholar 

  3. Hirano T. Interleukin 6 and its receptor: ten years later. Int Rev Immunol 1998; 16: 249.

    Article  CAS  PubMed  Google Scholar 

  4. Muraguchi A, Hirano T, Tang B, et al. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med 1988; 167: 332.

    Article  CAS  PubMed  Google Scholar 

  5. Lotz M, Jirik F, Kabouridis P, et al. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med 1988; 167: 1253.

    Article  CAS  PubMed  Google Scholar 

  6. Sachs L, Lotem J, Shabo Y. The molecular regulators of macrophage and granulocyte development. Ann N Y Acad Sci 1989; 557: 417.

    Article  CAS  PubMed  Google Scholar 

  7. Gröndal G, Gunnarsson I, Rönnelid J, Rogberg S, Klareskog L, Lundberg I. Cytokine production, serum levels and disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 1999; 18: 565.

    Google Scholar 

  8. Linker-Israeli M, Deans R, Wallace D, Prehn J, Ozeri-Chen T, Klinenberg J. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol 1991; 147: 117.

    CAS  PubMed  Google Scholar 

  9. Alheim K, Bartfai T, Interleukin-1 System: Receptors T. Ligands, and ICE in the Brain and Their Involvement in the Fever Response. Ann N Y Acad Sci 1998; 840: 51.

    Article  CAS  PubMed  Google Scholar 

  10. Bresnihan B, Cunnane G. Interleukin-1 receptor antagonist. Rheum Dis Clin North Am 1998; 24: 615.

    Article  CAS  PubMed  Google Scholar 

  11. Arend WP. Interleukin-1 receptor antagonist. Adv Immunol 1993; 54: 167.

    Article  CAS  PubMed  Google Scholar 

  12. Brugos B, Kiss E, Dul C, et al. Measurement of interleukin-1 receptor antagonist in patients with systemic lupus erythematosus could predict renal manifestation of the disease. Hum Immunol 2010; 71: 874.

    Article  CAS  PubMed  Google Scholar 

  13. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996; 87: 2095.

    CAS  PubMed  Google Scholar 

  14. Sturfelt G, Roux-Lombard P, Wollheim F, Dayer J. Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus. Rheumatology 1997; 36: 1283.

    Article  CAS  Google Scholar 

  15. Aringer M, Smolen J. Cytokine expression in lupus kidneys. Lupus 2005; 14: 13.

    Article  CAS  PubMed  Google Scholar 

  16. Barkhordari E, Rezaei N, Ansaripour B, et al. Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome. J Clin Immunol 2010; 30: 74.

    Article  CAS  PubMed  Google Scholar 

  17. Amirzargar A, Shahram F, Nikoopour E, et al. Proinflammatory cytokine gene polymorphisms in Behcet’s disease. Eur Cytokine Netw 2010; 21: 292.

    CAS  PubMed  Google Scholar 

  18. Mahdaviani SA, Rezaei N, Moradi B, Dorkhosh S, Amirzargar AA, Movahedi M. Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. J Clin Immunol 2009; 29: 57.

    Article  CAS  PubMed  Google Scholar 

  19. Rezaei N, Amirzargar AA, Shakiba Y, Mahmoudi M, Moradi B, Aghamohammadi A. Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency. Clin Exp Immunol 2009; 155: 21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Amirzargar AA, Bagheri M, Ghavamzadeh A, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet 2005; 32: 167.

    Article  CAS  PubMed  Google Scholar 

  21. Amirzargar AA, Rezaei N, Jabbari H, et al. Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis. Eur Cytokine Netw 2006; 17: 84.

    CAS  PubMed  Google Scholar 

  22. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.

    Article  CAS  PubMed  Google Scholar 

  23. Amirzargar AA, Naroueynejad M, Khosravi F, et al. Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw 2008; 19: 104.

    CAS  PubMed  Google Scholar 

  24. Miller S, Dykes D, Polesky H. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Amirzargar A, Bagheri M, Ghavamzadeh A, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet 2005; 32: 167.

    Article  CAS  PubMed  Google Scholar 

  26. Amirzargar A, Shahram F, Nikoopour E, et al. Proinflammatory cytokine gene polymorphisms in Behcet’s disease. Eur Cytokine Netw 2010; 21: 292.

    CAS  PubMed  Google Scholar 

  27. Amirzargar AA, Rezaei N, Jabbari H, et al. Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis. Eur Cytokine Netw 2006; 17: 84.

    CAS  PubMed  Google Scholar 

  28. Camargo J, Correa P, Castiblanco J, Anaya J. Interleukin-1β polymorphisms in Colombian patients with autoimmune rheumatic diseases. Genes Immun 2004; 5: 609.

    Article  CAS  PubMed  Google Scholar 

  29. Dinarello C. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 2002; 20: S1.

    CAS  PubMed  Google Scholar 

  30. Jandl RC, George JL, Dinarello CA, Schur PH. The effect of interleukin 1 on IgG synthesis in systemic lupus erythematosus. Clin Immunol Immunopathol 1987; 45: 384.

    Article  CAS  PubMed  Google Scholar 

  31. Iacoviello L, Di Castelnuovo A, Gattone M, et al. Polymorphisms of the interleukin-1β gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro. Arterioscler Thromb Vasc Biol 2005; 25: 222.

    CAS  PubMed  Google Scholar 

  32. Tahmasebi Z, Akbarian M, Mirkazemi S, et al. Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus. Rheumatol Int 2013; 33: 2591.

    Article  CAS  PubMed  Google Scholar 

  33. Parks C, Cooper G, Dooley M, et al. Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population based study in the southeastern United States. Ann Rheum Dis 2004; 63: 91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Tsai LJ, Hsiao SH, Tsai JJ, Lin CY, Tsai LM, Lan JL. Higher genetic susceptibility to inflammation in mild disease activity of systemic lupus erythematosus. Rheumatol Int 2009; 29: 1001.

    Article  CAS  PubMed  Google Scholar 

  35. Huang CM, Wu MC, Wu JY, Tsai FJ. Lack of association of interleukin-1β gene polymorphisms in Chinese patients with systemic lupus erythematosus. Rheumatol Int 2002; 21: 173.

    Article  CAS  PubMed  Google Scholar 

  36. Wang B, Zhu JM, Fan YG, et al. The association of IL1α and IL1β polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis. Gene 2013; 527: 95.

    Article  CAS  PubMed  Google Scholar 

  37. Tsai LJ, Lan JL, Lin CY, Hsiao SH, Tsai LM, Tsai JJ. The different expression patterns of interleukin-1 receptor antagonist in systemic lupus erythematosus. Tissue Antigens 2006; 68: 493.

    Article  CAS  PubMed  Google Scholar 

  38. Godarzi EM, Sarvestani EK, Aflaki E, Amirghofran Z. Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus. Clin Rheumatol 2011; 30: 179.

    Article  PubMed  Google Scholar 

  39. Schotte H, Schlüter B, Rust S, Assmann G, Domschke W, Gaubitz M. Interleukin-6 promoter polymorphism (−174 G/C) in Caucasian German patients with systemic lupus erythematosus. Rheumatology 2001; 40: 393.

    Article  CAS  PubMed  Google Scholar 

  40. Huang CM, Huo AP, Tsai CH, Chen CL, Tsai FJ. Lack of association of interleukin-6 and interleukin-8 gene polymorphisms in Chinese patients with systemic lupus erythematosus. J Clin Lab Anal 2006; 20: 255.

    Article  CAS  PubMed  Google Scholar 

  41. Guarnizo-Zuccardi P, Lopez Y, Giraldo M, et al. Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 2007; 70: 376.

    Article  CAS  PubMed  Google Scholar 

  42. Santos MJ, Fernandes D, Capela S, da Silva JC, Fonseca JE. Interleukin-6 promoter polymorphism −174 G/C is associated with nephritis in Portuguese Caucasian systemic lupus erythematosus patients. Clin Rheumatol 2011; 30: 409.

    Article  PubMed  Google Scholar 

  43. Hrycek A, Siekiera U, Cieslik P, Szkrobka W. HLA-DRB1-DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 2005; 26: 1.

    Article  CAS  PubMed  Google Scholar 

  44. Asano NM, Angelo HD, da Silva HA, Maia MM, Lins OG, Souza PE. Interleukin-6 promoter polymorphisms −174 GC in Brazilian patients with systemic lupus erythematosus. Hum Immunol 2013; 74: 1153.

    Article  CAS  PubMed  Google Scholar 

  45. Chua K, Kee B, Tan S, Lian L. Interleukin-6 promoter polymorphisms (−174 G/C) in Malaysian patients with systemic lupus erythematosus. Braz J Med Biol Res 2009; 42: 551.

    Article  CAS  PubMed  Google Scholar 

  46. Hristova M, Dourmishev L, Kamenarska Z, et al. Role of the Promoter Polymorphism IL-6 −174 G/C in Dermatomyositis and Systemic Lupus Erythematosus. Biomed Res Int 2013; 2013.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nima Rezaei.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ziaee, V., Tahghighi, F., Moradinejad, M.H. et al. Interleukin-6, interleukin-1 gene cluster and interleukin-1 receptor polymorphisms in Iranian patients with juvenile systemic lupus erythematosus. Eur Cytokine Netw 25, 35–40 (2014). https://doi.org/10.1684/ecn.2014.0352

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1684/ecn.2014.0352

Key words

Navigation