Skip to main content

Advertisement

SpringerLink
Log in

The Impact of Interleukin (IL)-33 Gene Polymorphisms and Environmental Factors on Risk of Asthma in the Iranian Population

  • ASTHMA
  • Published:
Lung Aims and scope Submit manuscript

Abstract

Background

Airway epithelial cells secrete Interleukin-33 in response to the different allergens. Several single nucleotide polymorphisms (SNP) of this cytokine have been reported to be involved in the development of asthma. We conducted this study to evaluate the impact of the two most common SNPs of the IL-33 gene (rs1342326 and rs3939286) and environmental factors on the susceptibility to asthma in the Iranian population.

Subjects and Methods

In this study, we enrolled 126 asthmatics patients and 300 age, sex-matched controls. Genotyping was performed by real-time PCR using the TaqMan SNP genotyping assay. Moreover, total serum IgE level, eosinophil count, and skin prick test were accomplished and complete history was taken from all the participants.

Results

The frequencies of mutant genotypes in both SNPs were significantly higher in asthmatics than controls. C/C genotype of rs1342326 [OR (95% CI) 2.50 (1.33–4.69)] and A/A genotype of rs3939286 [OR (95% CI) 2.18 (1.05–4.52)] were associated with higher risk of asthma development. While A/C+C/C genotype of rs1342326 was more prevalent in mild asthma [OR (95% CI) 2.36 (1.14–4.89)], G/A+A/A genotype of rs3939286 was associated with increased risk of moderate and severe asthma [OR (95% CI) 2.53 (1.30–4.94)].

Conclusion

This study revealed that both IL-33 SNPs were associated with an increased risk of asthma. The rs1342326 was associated with atopic, mild and adult-onset asthma and a higher level of eosinophils in peripheral blood. However, rs3939286 was more frequent in moderate and severe asthma. Moreover, rs3939286 was associated with non-atopic and childhood-onset asthma.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. de Benedictis D, Bush A (2017) Asthma in adolescence: is there any news? Pediatr Pulmonol 52(1):129–138. https://doi.org/10.1002/ppul.23498

    Article  PubMed  Google Scholar 

  2. Fazlollahi MR, Najmi M, Fallahnezhad M et al (2018) The prevalence of asthma in Iranian adults: the first national survey and the most recent updates. Clin Respir J 12(5):1872–1881. https://doi.org/10.1111/crj.12750

    Article  PubMed  Google Scholar 

  3. Masoli M, Fabian D, Holt S et al (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59(5):469–478. https://doi.org/10.1111/j.1398-9995.2004.00526.x

    Article  PubMed  Google Scholar 

  4. Varmaghani M, Rashidian A, Kebriaeezadeh A et al (2017) National and sub-national prevalence, trend, and burden of asthma in Iran from 1990 to 2013; the study protocol. Arch Iran Med 17(12):804–809.

    PubMed  Google Scholar 

  5. Liew FY, Girard JP, Turnquist HR (2016) Interleukin-33 in health and disease. Nat Rev Immunol 16(11):676–689. https://doi.org/10.1038/nri.2016.95

    Article  CAS  PubMed  Google Scholar 

  6. Khaitov MR, Gaisina AR, Shilovskiy IP et al (2018) The role of interleukin-33 in pathogenesis of bronchial asthma. New experimental data. Biochemistry (Mosc) 83(1):13–25. https://doi.org/10.1134/s0006297918010029

    Article  CAS  Google Scholar 

  7. Moffatt MF, Gut IG, Demenais F et al (2010) A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363(13):1211–1221. https://doi.org/10.1056/NEJMoa0906312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gudbjartsson DF, Bjornsdottir US, Halapi E et al (2009) Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet 41(3):342–347. https://doi.org/10.1038/ng.323

    Article  CAS  PubMed  Google Scholar 

  9. Belpinati F, Malerba G, Trabetti E et al (2011) Association of childhood allergic asthma with markers flanking the IL33 gene in Italian families. J Allergy Clin Immunol 128(3):667–668. https://doi.org/10.1016/j.jaci.2011.05.004

    Article  CAS  PubMed  Google Scholar 

  10. Savenije OE, Mahachie John JM, Granell R et al (2014) Association of IL33-IL-1 receptor-like 1 (IL1RL1) pathway polymorphisms with wheezing phenotypes and asthma in childhood. J Allergy Clin Immunol 134(1):170–177. https://doi.org/10.1016/j.jaci.2013.12.1080

    Article  CAS  PubMed  Google Scholar 

  11. Kabata H, Moro K, Koyasu S et al (2015) Group 2 innate lymphoid cells and asthma. Allergol Int 64(3):227–234. https://doi.org/10.1016/j.alit.2015.03.004

    Article  CAS  PubMed  Google Scholar 

  12. Saglani S, Lui S, Ullmann N et al (2013) IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma. J Allergy Clin Immunol 132(3):676–685.e13. https://doi.org/10.1016/j.jaci.2013.04.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li X, Ampleford EJ, Howard TD et al (2012) Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases. J Allergy Clin Immunol 130(4):861–8.e7. https://doi.org/10.1016/j.jaci.2012.04.041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Melen E, Himes BE, Brehm JM et al (2010) Analyses of shared genetic factors between asthma and obesity in children. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2010.06.030

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bousquet J, Clark TJ, Hurd S et al (2007) GINA guidelines on asthma and beyond. Allergy 62(2):102–112. https://doi.org/10.1111/j.1398-9995.2006.01305.x

    Article  CAS  PubMed  Google Scholar 

  16. American Thoracic Society (1995) Single-breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique—1995 update. Am J Respir Crit Care Med 152(6 Pt 1):2185–2198. https://doi.org/10.1164/ajrccm.152.6.8520796

    Article  Google Scholar 

  17. Assarehzadegan MA, Shakurnia AH, Amini A (2013) Sensitization to common aeroallergens among asthmatic patients in a tropical region affected by dust storm. J Med Sci 13(7):592–597. https://doi.org/10.3923/jms.2013.592.597

    Article  Google Scholar 

  18. Lung function protocol, data sheets and questionnaire (2014). https://www.ecrhs.org/quests.htm.

  19. Adult and child asthma call-back surveys questionnaires (2006). https://www.cdc.gov/asthma/pdfs/surveyquestions06.pdf.

  20. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16(3):1215.

    Article  CAS  Google Scholar 

  21. Charrad R, Kaabachi W, Berraies A et al (2018) IL-33 gene variants and protein expression in pediatric Tunisian asthmatic patients. Cytokine 104:85–91. https://doi.org/10.1016/j.cyto.2017.09.028

    Article  CAS  PubMed  Google Scholar 

  22. Tulah AS, Holloway JW, Sayers I (2013) Defining the contribution of SNPs identified in asthma GWAS to clinical variables in asthmatic children. BMC Med Genet 14:100. https://doi.org/10.1186/1471-2350-14-100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cayrol C, Girard JP (2018) Interleukin-33 (IL-33): a nuclear cytokine from the IL-1 family. Immunol Rev 281(1): 154–168. https://doi.org/10.1111/imr.12619

    Article  CAS  PubMed  Google Scholar 

  24. Cayrol C, Girard JP (2014) IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. Curr Opin Immunol 31:31–37. https://doi.org/10.1016/j.coi.2014.09.004

    Article  CAS  PubMed  Google Scholar 

  25. Li Y, Wang W, Lv Z et al (2018) Elevated expression of IL-33 and TSLP in the airways of human asthmatics in vivo: a potential biomarker of severe refractory disease. J Immunol 200(7):2253–2262. https://doi.org/10.4049/jimmunol.1701455

    Article  CAS  PubMed  Google Scholar 

  26. Karta MR, Broide DH, Doherty TA (2016) Insights into group 2 innate lymphoid cells in human airway disease. Curr Allergy Asthma Rep 16(1):8. https://doi.org/10.1007/s11882-015-0581-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tan DJ, Walters EH, Perret JL et al (2015) Age-of-asthma onset as a determinant of different asthma phenotypes in adults: a systematic review and meta-analysis of the literature. Expert Rev Respir Med 9(1):109–123. https://doi.org/10.1586/17476348.2015.1000311

    Article  CAS  PubMed  Google Scholar 

  28. Peters SP (2014) Asthma phenotypes: nonallergic (intrinsic) asthma. J Allergy Clin Immunol Pract 2(6):650–652. https://doi.org/10.1016/j.jaip.2014.09.006

    Article  PubMed  Google Scholar 

  29. Schatz M, Rosenwasser L (2014) The allergic asthma phenotype. J Allergy Clin Immunol Pract 2(6):645–648. https://doi.org/10.1016/j.jaip.2014.09.004

    Article  PubMed  Google Scholar 

  30. Le Moual N, Zock JP, Dumas O et al (2018) Update of an occupational asthma-specific job exposure matrix to assess exposure to 30 specific agents. Occup Environ Med 75(7):507–514. https://doi.org/10.1136/oemed-2017-104866

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The current study was supported by a grant (Grant Number 5232) from medical Faculty, Iran University of Medical Sciences, Tehran, Iran.

Author information

Author notes

  1. Mojdeh Matloubi and Maral Ranjbar contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Immunology, School of Medicine, Iran University of Medical Science, Hemmat Highway, Tehran, Iran

    Mojdeh Matloubi, Maral Ranjbar & Fatemeh Sadeghi

  2. Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Science, Tehran, Iran

    Mohammad-Ali Assarehzadegan

  3. Immunology Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mohammad-Ali Assarehzadegan

  4. Department of Allergy and Clinical Immunology, Iran University of Medical Sciences, Tehran, Iran

    Morteza Fallahpour

  5. Firoozabadi Hospital, Iran University of Medical Sciences, Tehran, Iran

    Morteza Fallahpour

  6. Digestive Diseases Research Core Center, Division of Gastroenterology, School of Medicine, Washington University, St. Louis, USA

    Saeed Soleyman-Jahi

  7. Department of Biostatistics, School of Public Health, Iran University of Medical Science, Tehran, Iran

    Leila Janani

Authors
  1. Mojdeh Matloubi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maral Ranjbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad-Ali Assarehzadegan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Morteza Fallahpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fatemeh Sadeghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Saeed Soleyman-Jahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leila Janani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Concept & Design: AMA, MM, RM. Data Collection and/or Processing: MM, RM, FM. Analysis and/or Interpretation: MM, RM, SF, SJS, JL. Writing: MM, SF, SJS, RM. Final approval: AMA, MM, RM, SF, SJS, FM, JL.

Corresponding author

Correspondence to Mohammad-Ali Assarehzadegan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matloubi, M., Ranjbar, M., Assarehzadegan, MA. et al. The Impact of Interleukin (IL)-33 Gene Polymorphisms and Environmental Factors on Risk of Asthma in the Iranian Population. Lung 198, 105–112 (2020). https://doi.org/10.1007/s00408-019-00301-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-019-00301-9

Keywords

Search

Navigation