Clinical Rheumatology

, Volume 30, Issue 2, pp 179–184 | Cite as

Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus

  • Esmaeil Moazemi Godarzi
  • Eskandar Kamali Sarvestani
  • Elham Aflaki
  • Zahra Amirghofran
Original Article


Interleukin 6 (IL-6) has been shown to be related to the pathogenesis of systemic lupus erythematosus (SLE). In the present study, the relationship between two polymorphisms in the promoter region of IL-6 gene at positions −572 G/C and −174 G/C and disease susceptibility in 401 Iranian patients with SLE was investigated using polymerase chain reaction–restriction fragment length polymorphism method. The genotype distribution and allele frequencies of IL-6 gene polymorphism at −174 position showed no significant difference between SLE patients and controls. In contrary, both allelic and genotypic frequencies at the −572 position significantly differed in SLE patients and controls. At this position, GG genotype was observed in 77.9% of patients compared to 68.9% in the control group (p < 0.014). The frequency of −572 G allele in patients (87.3%) was also higher than in controls (83.2%; p = 0.034). The haplotype study showed no significant difference between patients and healthy subjects. Study of the relationship between these polymorphisms and clinical manifestations and laboratory parameters showed an association between −174 polymorphism and the presence of antinuclear antibodies in all patients and rash and hematuria in male patients (p < 0.04). At −572 polymorphism, a significant difference with regard to photosensitivity in male patients (p = 0.04) was found. In conclusion, results of this study showed that −572 polymorphism plays an important role in susceptibility to SLE and that −174 polymorphism could influence the presence of antinuclear antibodies in the patients.


IL-6 gene polymorphism Systemic lupus erythematosus 



This work was supported by grant no. 2929 from Shiraz University of Medical Sciences.




  1. 1.
    Selmi C (2009) A new year in autoimmunity. Ann N Y Acad Sci 1173:239–242CrossRefPubMedGoogle Scholar
  2. 2.
    Lau CS, Yin G, Mok MY (2006) Ethnic and geographical differences in systemic lupus erythematosus: an overview. Lupus 15(11):715–719CrossRefPubMedGoogle Scholar
  3. 3.
    Hostmann A, Jacobi AM, Mei H, Hiepe F, Dörner T (2008) Peripheral B cell abnormalities and disease activity in systemic lupus erythematosus. Lupus 17(12):1064–1069CrossRefPubMedGoogle Scholar
  4. 4.
    Segal R, Bermas BL, Dayan M, Kalush F, Shearer GM, Mozes E (1997) Kinetics of cytokine production in experimental systemic lupus erythematosus: involvement of T helper cell 1/T helper cell 2-type cytokines in disease. J Immunol 158(6):3009–3016PubMedGoogle Scholar
  5. 5.
    Fairhurst AM, Wandstrat AE, Wakeland EK (2006) Systemic lupus erythematosus: multiple immunological phenotypes in a complex genetic disease. Adv Immunol 92:1–69CrossRefPubMedGoogle Scholar
  6. 6.
    Rhodes B, Vyse TJ (2008) The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford) 47911:1603–1611CrossRefGoogle Scholar
  7. 7.
    Rahman A (2003) Cytokines in systemic lupus erythematosus, London, UK. Arthritis Res Ther 5(4):160–164CrossRefPubMedGoogle Scholar
  8. 8.
    Maeda K, Malykhin A, Teague-Weber BN, Sun XH, Farris AD, Coggeshall KM (2009) Interleukin-6 aborts lymphopoiesis and elevates production of myeloid cells in systemic lupus erythematosus-prone B6.lSle1.Yaa animals. Blood 113(19):4534–4540CrossRefPubMedGoogle Scholar
  9. 9.
    Fonseca JE, Santos MJ, Canhão H, Choy E (2009) Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 8(7):538–542CrossRefPubMedGoogle Scholar
  10. 10.
    Linker-Israeli M, Wallace DJ, Prehn J, Michael D, Honda M, Taylor KD, Paul-Labrador M, Fischel-Ghodsian N, Fraser PA, Klinenberg JR (1999) Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression. Genes Immun 1(1):45–52CrossRefPubMedGoogle Scholar
  11. 11.
    Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH (2007) Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 27(5):461–466CrossRefPubMedGoogle Scholar
  12. 12.
    Liang B, Gardner DB, Griswold DE, Bugelski PJ, Song XY (2006) Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus. Immunology 119(3):296–305CrossRefPubMedGoogle Scholar
  13. 13.
    Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) 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. Clin Invest 102(7):1369–1376CrossRefGoogle Scholar
  14. 14.
    Morse HR, Olomolaiye OO, Wood NA, Keen LJ, Bidwell JL (1999) Induced heteroduplex genotyping of TNF-alpha, IL-1beta, IL-6 and IL-10 polymorphisms associated with transcriptional regulation. Cytokine 11(10):789–795CrossRefPubMedGoogle Scholar
  15. 15.
    Olomolaiye O, Wood NA, Bidwell JL (1998) A novel NlaIII polymorphism in the human IL-6 promoter. Eur J Immunogenet 25(2–3):267PubMedGoogle Scholar
  16. 16.
    Osiri M, McNicholl J, Moreland LW, Bridges SL Jr (1999) A novel single nucleotide polymorphism and five probable haplotypes in the 5′ flanking region of the IL-6 gene in African-Americans. Genes Immun 1(2):166–167CrossRefPubMedGoogle Scholar
  17. 17.
    Córdoba-Lanús E, de-Torres JP, López-Aguilar C, Rodríguez-Pérez MC, Maca-Meyer N, Montejo-de-Garcini A, Aguirre-Jaime A, Pérez-Méndez L, Casanova C (2008) Association of IL-6 gene polymorphisms and COPD in a Spanish population. Respir Med 102(12):1805–1811CrossRefPubMedGoogle Scholar
  18. 18.
    Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M (2001) Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL-6 gene in primary Sjögren's syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford) 40(6):656–661CrossRefGoogle Scholar
  19. 19.
    DeMichele A, Martin AM, Mick R, Gor P, Wray L, Klein-Cabral M, Athanasiadis G, Colligan T, Stadtmauer E, Weber B (2003) Interleukin-6 −174G→C polymorphism is associated with improved outcome in high-risk breast cancer. Cancer Res 63(32):8051–8056PubMedGoogle Scholar
  20. 20.
    Ogilvie EM, Fife MS, Thompson SD, Twine N, Tsoras M, Moroldo M, Fisher SA, Lewis CM, Prieur AM, Glass DN, Woo P (2003) The -174G allele of the interleukin-6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic arthritis families. Arthritis Rheum 48(11):3202–3206CrossRefPubMedGoogle Scholar
  21. 21.
    Kristiansen OP, Nolsøe RL, Larsen L, Gjesing AM, Johannesen J, Larsen ZM, Lykkesfeldt AE, Karlsen AE, Pociot F, Mandrup-Poulsen T, DIEGG, DSGD (2003) Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females. Hum Mol Genet 12(10):1101–1110CrossRefPubMedGoogle Scholar
  22. 22.
    Hrycek A, Siekiera U, Cieślik P, Szkróbka W (2005) HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 26(1):1–6CrossRefPubMedGoogle Scholar
  23. 23.
    Schotte H, Schlüter B, Rust S, Assmann G, Domschke W, Gaubitz M (2001) Interleukin-6 promoter polymorphism (–174 G/C) in Caucasian German patients with systemic lupus erythematosus. Rheumatology (Oxford) 40(4):393–400CrossRefGoogle Scholar
  24. 24.
    Yang G, Liu H, Jiang M, Jiang X, Li S, Yuan Y, Ma D (1998) Experimental study on intramuscular injection of eukaryotic expression vector pcDNA3- IL-6 on BXSB mice. Chin Med J (Engl) 111(1):38–42Google Scholar
  25. 25.
    Huang CM, Huo AP, Tsai CH, Chen CL, Tsai FJ (2006) Lack of association of interleukin-6 and interleukin-8 gene polymorphisms in Chinese patients with systemic lupus erythematosus. J Clin Lab Anal 20(6):255–259CrossRefPubMedGoogle Scholar
  26. 26.
    Guarnizo-Zuccardi P, Lopez Y, Giraldo M, Garcia N, Rodriguez L, Ramirez L, Uribe O, Garcia L, Vasquez G (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70(5):376–382CrossRefPubMedGoogle Scholar
  27. 27.
    Müller-Steinhardt M, Fricke L, Müller B, Ebel B, Kirchner H, Härtel C (2004) Cooperative influence of the interleukin-6 promoter polymorphisms −597, −572 and −174 on long-term kidney allograft survival. Am J Transplant 4(3):402–406CrossRefPubMedGoogle Scholar
  28. 28.
    Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275(24):18138–18144CrossRefPubMedGoogle Scholar
  29. 29.
    Brull DJ, Montgomery HE, Sanders J, Dhamrait S, Luong L, Rumley A, Lowe GD, Humphries SE (2001) Interleukin-6 gene −174g>c and −572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 21(9):1458–1463CrossRefPubMedGoogle Scholar
  30. 30.
    Bennermo M, Held C, Green F, Strandberg LE, Ericsson CG, Hansson LO, Watkins H, Hamsten A, Tornvall P (2004) Prognostic value of plasma interleukin-6 concentrations and the −174 G > C and −572 G > C promoter polymorphisms of the interleukin-6 gene in patients with acute myocardial infarction treated with thrombolysis. Atherosclerosis 174(1):157–163CrossRefPubMedGoogle Scholar
  31. 31.
    Panoulas VF, Stavropoulos-Kalinoglou A, Metsios GS, Smith JP, Milionis HJ, Douglas KM, Nightingale P, Kitas GD (2008) Association of interleukin-6 (IL-6) −174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis 204(1):178–183CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang D, Zhou Y, Wu L, Wang S, Zheng H, Yu B, Li J (2008) Association of IL-6 gene polymorphisms with cachexia susceptibility and survival time of patients with pancreatic cancer. Ann Clin Lab Sci 38(2):113–119PubMedGoogle Scholar
  33. 33.
    Chen RH, Chang CT, Chen WC, Tsai CH, Tsai FJ (2006) Proinflammatory cytokine gene polymorphisms among Hashimoto's thyroiditis patients. J Clin Lab Anal 20(6):260–265CrossRefPubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Esmaeil Moazemi Godarzi
    • 1
  • Eskandar Kamali Sarvestani
    • 1
    • 2
  • Elham Aflaki
    • 2
    • 3
  • Zahra Amirghofran
    • 1
    • 2
    • 4
  1. 1.Immunology Department, Medical SchoolShiraz University of Medical SciencesShirazIran
  2. 2.Autoimmune Disease Research CenterShiraz University of Medical SciencesShirazIran
  3. 3.Department of Internal medicineShiraz University of Medical SciencesShirazIran
  4. 4.Medicinal and Natural Products Chemistry Research CenterShiraz University of Medical SciencesShirazIran

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