Skip to main content

Advertisement

SpringerLink
Log in

Cytokine gene polymorphism and asthma susceptibility, progress and control level

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Asthma is a multifactor inflammatory disorder, and its management requires understanding of its various pathogenesis and control mechanisms. Cytokines and other inflammatory mediators are important factors in asthma pathophysiology. In this study, we evaluated the role of cytokine polymorphisms in the asthma susceptibility, progress, control, and lung functions. IL-4-C590T polymorphism by PCR-RFLP method, IFN-γ T+874A, TNF-α-A308G, IL-6 G−174C and TGF-β T+869C variants by ARMS-PCR method and IgE serum level by ELISA technique were determined in 81 asthmatic patients and 124 normal subjects. Asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. TNF-α−308GA genotype was more frequent in asthmatics (P = 0.025, OR 3.352), and polymorphisms between different asthma control levels (P > 0.05) were not different. IFN-γ+874AT genotype had a positive correlation with the familial history of asthma (P = 0.034, OR 2.688). IL-6−174C allele (P = 0.045), TNF-α−308GG genotype (P = 0.002) and TNF-α−308G allele (P = 0.004) showed reduced values, and TNF-α−308GA genotype (P = 0.002) increased FEF25-75 value in asthmatics. IFN-γ+874AA genotype caused a decrease in FVC factor (P = 0.045). This study showed that TNF-α−308GA is a risk factor for asthma, but cytokine gene variants do not affect asthma control and IgE serum levels. Variants producing lower levels of IL-6, TNF-α and IFN-γ are associated with reduced pulmonary capacities. To achieve an appropriate schema for asthma management, further studies with consideration of different aspects in a larger group of patients would be more elucidative.

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

Similar content being viewed by others

References

  1. Basehore MJ, Howard TD, Lange LA, Moore WC, Hawkins GA, Marshik PL, Harkins MS, Meyers DA, Bleecker ER (2004) A comprehensive evaluation of IL4 variants in ethnically diverse populations: association of total serum IgE levels and asthma in white subjects. J Allergy Clin Immunol 114:80–84

    Article  PubMed  CAS  Google Scholar 

  2. Aoki T, Hirota T, Tamar M, Ichikawa K, Takeda K, Arinami T, Shibasaki M, Noguchi E (2006) An association between asthma and TNF-308G/A polymorphism: meta-analysis. J Hum Genet 51:677–685

    Article  PubMed  CAS  Google Scholar 

  3. Barnes PJ (2002) The role of inflammation and anti-inflammatory medication in asthma. Respir Med 96(Suppl A):S9–S15

    PubMed  Google Scholar 

  4. Ngoc PL, Gold DR, Tzianabos AO, Weiss ST, Celedon JC (2005) Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol 5:161–166

    Article  PubMed  CAS  Google Scholar 

  5. Afshari JT, Farid-Hosseini R, Farahabadi SH, Heydarian F, Boskabady MH, Khoshnavaz R, Razavi A, Karimiani EG, Ghasemi G (2007) Association of the expression of IL-4 and IL-13 genes, IL-4 and IgE serum levels with allergic asthma. Iran J Allergy Asthma Immunol 6:67–72

    CAS  Google Scholar 

  6. Wang J, Xu Y, Zhao H, Sui H, Liang H, Jiang X (2009) Genetic variations in chemoattractant receptor expressed on Th2 cells (CRTH2) is associated with asthma susceptibility in Chinese children. Mol Biol Rep 36:1549–1553

    Article  PubMed  CAS  Google Scholar 

  7. De Vries JE, Carballido JM, Aversa G (1999) Receptors and cytokines involved in allergic TH2 cell responses. J Allergy Clin Immunol 103:S492–S496

    Article  PubMed  Google Scholar 

  8. Joseph J, Benedict S, Badrinath P, Wassef S, Joseph M, Abdulkhalik S, Nicholls MG (2003) Elevation of plasma transforming growth factor beta 1 levels in stable nonatopic asthma. Ann Allergy Asthma Immunol 91:472–476

    Article  PubMed  CAS  Google Scholar 

  9. Minshall EM, Leung DY, Martin RJ, Song YL, Cameron L, Ernst P, Hamid Q (1997) Eosinophil-associated TGF-b1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 17:326–333

    PubMed  CAS  Google Scholar 

  10. Thomas PS (2001) Tumour necrosis factor-alpha: the role of this multifunctional cytokine in asthma. Immunol Cell Biol 79:132–140

    Article  PubMed  CAS  Google Scholar 

  11. Russo C, Polosa R (2005) TNF-α as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis. Clin Sci 109:135–142

    Article  PubMed  CAS  Google Scholar 

  12. Deetz DC, Jagielo PJ, Quinn TJ, Thorne PS, Bleuer SA, Schwartz DA (1997) The kinetics of grain dust-induced inflammation of the lower respiratory tract. Am J Respir Crit Care Med 155:254–259

    PubMed  CAS  Google Scholar 

  13. Lacy P, Schaffer FL, Mahmudi-Azer S, Bablitz B, Hagen SC, Velazquez J, Kay AB, Moqbel R (1998) Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics and effects of interferon gamma. Blood 91:2508–2516

    PubMed  CAS  Google Scholar 

  14. Imboden M, Nieters A, Bircher AJ, Brutsche M, Becker N, Wjst M, Ackermann-Liebrich U, Berger W, Probst-Hensch NM (2006) Cytokine gene polymorphisms and atopic disease in two European cohorts (ECRHS-Basel and SAPALDIA). Clin Mol Allergy 4:1–9

    Article  Google Scholar 

  15. Gupta V, Sehajpal PK (2003) Rapid detection of single nucleotide (−308) polymorphism in TNF-a promoter using ARMS-PCR. Curr Sci 85:1521–1523

    CAS  Google Scholar 

  16. 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. J Clin Invest 102:1369–1376

    Article  PubMed  CAS  Google Scholar 

  17. Arkwright PD, Chase JM, Babbage S, Pravica V, David TJ, Hutchinson IV (2001) Atopic dermatitis is associated with a low-producer transforming growth factor β1 cytokine genotype. J Allergy Clin Immunol 108:281–284

    Article  PubMed  CAS  Google Scholar 

  18. Kamali-Sarvestani E, Zolghadri J, Gharesi-Fard B, Sarvari J (2005) Cytokine gene polymorphisms and susceptibility to recurrent pregnancy loss in Iranian women. J Reprod Immunol 65:171–178

    Article  PubMed  CAS  Google Scholar 

  19. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2006. http://www.ginasthma.org. Accessed 21 March 2007

  20. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. http://www.asthmacontrol.com. Accessed 20 July 2007

  21. Karimi MH, Daneshmandi S, Pourfathollah AA, Geramizadeh B, Malekhosseini SA, Nikeghbalian S, Yaghobi R, Bolandparvaz S (2010) Association of IL-6 promoter and IFN-γ gene polymorphisms with acute rejection of liver transplantation. Mol Biol Rep. doi:10.1007/s11033-010-0572-6

  22. Schmidt J, Fleissner S, Heimann-Weitschat I, Lindstaedt R, Pomberg B, Werner U, Szelenyi I (1997) Effect of corticosteroids, cyclosporin A, and methotrexate on cytokine release from monocytes and T-cell subsets. Immunopharmacology 27:173–179

    Article  Google Scholar 

  23. Tamaoki J, Kondo M, Sakai N, Aoshiba K, Tagaya E, Nakata J, Isono K, Nagai A (2000) Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid dependent asthma: a double-blind randomized study. Lancet 356:273–278

    Article  PubMed  CAS  Google Scholar 

  24. Mak JC, Leung HC, Ho SP, Law BK, Ho AS, Lam WK, Ip MS, Chan-Yeung MM (2006) Analysis of TGF-b1 gene polymorphisms in Hong Kong Chinese patients with asthma. J Allergy Clin Immunol 117:92–96

    Article  PubMed  CAS  Google Scholar 

  25. Seow A, Ng DP, Choo S, Eng P, Poh WT, Ming T, Wan YT (2006) Joint effect of asthma/atopy and an IL-6 gene polymorphism on lung cancer risk among lifetime non-smoking Chinese women. Carcinogenesis 27:1240–1244

    Article  PubMed  CAS  Google Scholar 

  26. Miller GE, Gaudin A, Zysk E, Chen E (2009) Parental support and cytokine activity in childhood asthma: the role of glucocorticoid sensitivity. J Allergy Clin Immunol 123:824–830

    Article  PubMed  CAS  Google Scholar 

  27. Castro J, Telleria JJ, Linares P, Blanco-Quiros A (2000) Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients. J Investig Allergol Clin Immunol 10:149–154

    PubMed  CAS  Google Scholar 

  28. Settin A, Zedan M, Farag M, Ezz El Regal M, Osman E (2008) Gene polymorphisms of IL-6−174 G/C and IL-1Ra VNTR in asthmatic children. Indian J Pediatr 75:1019–1024

    Article  PubMed  Google Scholar 

  29. Valletta EA, Piacentini GL, Del Col G, Boner AL (1997) FEF25–75 as a marker of airway obstruction in asthmatic children during reduced mite exposure at high altitude. J Asthma 34:127–131

    Article  PubMed  CAS  Google Scholar 

  30. Lebecque P, Kiakulanda P, Coates AL (1993) Spirometry in the asthmatic child: is FEF25–75 a more sensitive test than FEV1/FVC? Pediatr Pulmonol 16:19–22

    Article  PubMed  CAS  Google Scholar 

  31. Shin HD, Park BL, Kim LH, Jung JH, Wang HJ, Kim YJ, Park HS, Hong SJ, Choi BW, Kim DJ, Park CS (2004) Association of tumor necrosis factor (TNF) polymorphisms with asthma and serum total IgE. Hum Mol Genet 13:397–403

    Article  PubMed  CAS  Google Scholar 

  32. Ueda T, Niimi A, Matsumoto H, Takemura M, Yamaguchi M, Matsuoka H, Jinnai M, Chin K, Minakuchi M, Lei C, Shirakawa T, Mishima M (2008) TGFβ1 promoter polymorphism C-509T and pathophysiology of asthma. J Allergy Clin Immunol 121:659–664

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors are grateful to the Department of Immunology of Tarbiat Modares University for financial support.

Author information

Authors and Affiliations

  1. Department of Immunology, Tarbiat Modares University, Faculty of Medical Sciences, Tehran, Iran

    Saeed Daneshmandi, Ali Akbar Pourfathollah & Parisa Amir Kalvanagh

  2. Asthma and Allergy Research Institute, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Zahra Pourpak

  3. TB and Lung Disease Research Cancer, NRITLD, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hasan Heidarnazhad

Authors
  1. Saeed Daneshmandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Akbar Pourfathollah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zahra Pourpak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hasan Heidarnazhad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Parisa Amir Kalvanagh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali Akbar Pourfathollah.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 48 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Daneshmandi, S., Pourfathollah, A.A., Pourpak, Z. et al. Cytokine gene polymorphism and asthma susceptibility, progress and control level. Mol Biol Rep 39, 1845–1853 (2012). https://doi.org/10.1007/s11033-011-0927-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-0927-7

Keywords

Search

Navigation