Skip to main content
SpringerLink
Log in

Interleukin-18 promoter polymorphism and asthma risk: a meta-analysis

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Some studies have shown that IL-18 was associated with aetiology and progression of asthma. However, the association between single-nucleotide polymorphisms −607C/A (rs1946518) and −137G/C (rs187238) located in the IL-18 gene promoter and asthma risk was still controversial and ambiguous. To derive a more precise effect on the association between these polymorphisms and asthma risk, we performed a meta-analysis based on the currently available evidence of the literature. A total of 5 studies with 1411 cases and 1525 controls for −607C/A polymorphism and 5 studies with 1883 cases and 6645 controls for −137G/C polymorphism were identified to perform a meta-analysis, up to October 2010. Summary ORs and corresponding 95% CIs for IL-18 polymorphisms and asthma were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were evaluated. We found that individuals carrying AC/CC genotype of −607C/A polymorphism were associated with an increased asthma risk in recessive model (OR = 1.278; 95% CI, 1.073–1.522). However, no significant association was observed between −137G/C polymorphism and asthma risk under different contrast models. There was no evidence of publication bias. The present meta-analysis suggested that IL-18 −607C/A polymorphism in promoter region was associated with asthma risk.

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

Similar content being viewed by others

References

  1. Chang JT, Segal BM, Nakanishi K, Okamura H, Shevach EM (2000) The costimulatory effect of IL-18 on the induction of antigen-specific IFN-gamma production by resting T cells is IL-12 dependent and is mediated by up-regulation of the IL-12 receptor beta2 subunit. Eur J Immunol 30:1113–1119

    PubMed  CAS  Google Scholar 

  2. Izakovicova Holla L (2003) Interleukin-18 in asthma and other allergies. Clin Exp Allergy 33:1023–1025

    PubMed  CAS  Google Scholar 

  3. Tanaka H, Miyazaki N, Oashi K, Teramoto S, Shiratori M, Hashimoto M, Ohmichi M, Abe S (2001) IL-18 might reflect disease activity in mild and moderate asthma exacerbation. J Allergy Clin Immunol 107:331–336

    PubMed  CAS  Google Scholar 

  4. Wong CK, Ho CY, Ko FW, Chan CH, Ho AS, Hui DS, Lam CW (2001) Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol 125:177–183

    PubMed  CAS  Google Scholar 

  5. Orfali RL, Sato MN, Takaoka R, Azor MH, Rivitti EA, Hanifin JM, Aoki V (2009) Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion. Exp Dermatol 18:628–633

    PubMed  CAS  Google Scholar 

  6. Vercelli D (2008) Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol 8:169–182

    PubMed  CAS  Google Scholar 

  7. Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK, von Mutius E (2006) IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol 117:269–274

    PubMed  CAS  Google Scholar 

  8. Lee CC, Lin WY, Wan L, Tsai Y, Tsai CH, Huang CM, Chen CP, Tsai FJ (2008) Association of interleukin-18 gene polymorphism with asthma in Chinese patients. J Clin Lab Anal 22:39–44

    PubMed  CAS  Google Scholar 

  9. Koppelman GH, Stine OC, Xu J, Howard TD, Zheng SL, Kauffman HF, Bleecker ER, Meyers DA, Postma DS (2002) Genome-wide search for atopy susceptibility genes in Dutch families with asthma. J Allergy Clin Immunol 109:498–506

    PubMed  CAS  Google Scholar 

  10. Nolan KF, Greaves DR, Waldmann H (1998) The human interleukin 18 gene IL18 maps to 11q22.2–q22.3, closely linked to the DRD2 gene locus and distinct from mapped IDDM loci. Genomics 51:161–163

    PubMed  CAS  Google Scholar 

  11. Lachheb J, Chelbi H, Ammar J, Hamzaoui K, Hamzaoui A (2008) Promoter polymorphism of the IL-18 gene is associated with atopic asthma in Tunisian children. Int J Immunogenet 35:63–68

    PubMed  CAS  Google Scholar 

  12. Haus-Seuffert P, Meisterernst M (2000) Mechanisms of transcriptional activation of cAMP-responsive element-binding protein CREB. Mol Cell Biochem 212:5–9

    PubMed  CAS  Google Scholar 

  13. 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

    PubMed  CAS  Google Scholar 

  14. Shin HD, Kim LH, Park BL, Choi YH, Park HS, Hong SJ, Choi BW, Lee JH, Park CS (2005) Association of interleukin 18 (IL18) polymorphisms with specific IgE levels to mite allergens among asthmatic patients. Allergy 60:900–906

    PubMed  CAS  Google Scholar 

  15. Giedraitis V, He B, Huang WX, Hillert J (2001) Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J Neuroimmunol 112:146–152

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    PubMed  Google Scholar 

  18. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  21. Harada M, Obara K, Hirota T, Yoshimoto T, Hitomi Y, Sakashita M, Doi S, Miyatake A, Fujita K, Enomoto T, Taniguchi M, Higashi N, Fukutomi Y, Nakanishi K, Nakamura Y, Tamari M (2009) A functional polymorphism in IL-18 is associated with severity of bronchial asthma. Am J Respir Crit Care Med 180:1048–1055

    PubMed  CAS  Google Scholar 

  22. Pawlik A, Kaminski M, Kusnierczyk P, Kurzawski M, Dziedziejko V, Adamska M, Safranow K, Gawronska-Szklarz B (2007) Interleukin-18 promoter polymorphism in patients with atopic asthma. Tissue Antigens 70:314–318

    PubMed  CAS  Google Scholar 

  23. Heinzmann A, Gerhold K, Ganter K, Kurz T, Schuchmann L, Keitzer R, Berner R, Deichmann KA (2004) Association study of polymorphisms within interleukin-18 in juvenile idiopathic arthritis and bronchial asthma. Allergy 59:845–849

    PubMed  CAS  Google Scholar 

  24. Imboden M, Nicod L, Nieters A, Glaus E, Matyas G, Bircher AJ, Ackermann-Liebrich U, Berger W, Probst-Hensch NM (2006) The common G-allele of interleukin-18 single-nucleotide polymorphism is a genetic risk factor for atopic asthma. The SAPALDIA Cohort Study. Clin Exp Allergy 36:211–218

    PubMed  CAS  Google Scholar 

  25. Leite-De-Moraes MC, Hameg A, Pacilio M, Koezuka Y, Taniguchi M, Van Kaer L, Schneider E, Dy M, Herbelin A (2001) IL-18 enhances IL-4 production by ligand-activated NKT lymphocytes: a pro-Th2 effect of IL-18 exerted through NKT cells. J Immunol 166:945–951

    PubMed  CAS  Google Scholar 

  26. Hoshino T, Wiltrout RH, Young HA (1999) IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response. J Immunol 162:5070–5077

    PubMed  CAS  Google Scholar 

  27. Yoshimoto T, Mizutani H, Tsutsui H, Noben-Trauth N, Yamanaka K, Tanaka M, Izumi S, Okamura H, Paul WE, Nakanishi K (2000) IL-18 induction of IgE: dependence on CD4 + T cells, IL-4 and STAT6. Nat Immunol 1:132–137

    PubMed  CAS  Google Scholar 

  28. Wild JS, Sigounas A, Sur N, Siddiqui MS, Alam R, Kurimoto M, Sur S (2000) IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. J Immunol 164:2701–2710

    PubMed  CAS  Google Scholar 

  29. Kruse S, Kuehr J, Moseler M, Kopp MV, Kurz T, Deichmann KA, Foster PS, Mattes J (2003) Polymorphisms in the IL 18 gene are associated with specific sensitization to common allergens and allergic rhinitis. J Allergy Clin Immunol 111:117–122

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project supported by Scientific Research Fund of Sichuan Provincial Education Department under Grant Nos: 2006B029 and 10ZA079.

Conflict of interest

None

Author information

Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Ying Ma

  2. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Ying Ma & Guo-Guang Peng

  3. Department of Forensic Medicine, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Bo Zhang & Yun Liu

  4. Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Ren-Kuan Tang

Authors
  1. Ying Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ren-Kuan Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guo-Guang Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yun Liu.

Additional information

Y. Ma and B. Zhang are contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 23 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ma, Y., Zhang, B., Tang, RK. et al. Interleukin-18 promoter polymorphism and asthma risk: a meta-analysis. Mol Biol Rep 39, 1371–1376 (2012). https://doi.org/10.1007/s11033-011-0871-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-0871-6

Keywords

Search

Navigation