Evaluation of the Frequency of Gene Polymorphism of Interleukin-7 Receptor Subunit Alpha (IL7R-α) in Atopic Patients and Healthy Controls

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

4 Subspecialist in Asthma, Allergy and Clinical Immunology, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Atopy and/or allergy are in the same meaning. Patients with allergy are individuals who have positive family history and the number of eosinophil in their blood test and immunoglobulin E (IgE) level in their skin test are high against allergen, which is demonstrated by allergic rhinitis, eczema, asthma and urticaria. Many genetic factors are involved in disease onset one of which is interleukin-7 receptor subunit alpha (IL7R-α). In this study we aimed to evaluate the frequency of this polymorphism in two groups of case and control.Methods: 101 patients with allergy and 201 controls were selected. After DNA extraction, different genotypes of C/T polymorphisms were studied using high-resolution melt real-time polymerase chain reaction (HRM real-time PCR) technique.Findings: There was a significant association between the frequency of this gene polymorphism and atopy. In fact, individuals with TT genotype were approximately 4 times more at a risk of this disease.Conclusion: The frequency of this polymorphism with same results was also studied in both Germany and India, which shows that this polymorphism is significantly associated with allergy. Studies have also shown that IL-7 plays a pivotal role not only in eosinophil survival and operation but also in immune system homeostasis.

Keywords

References

  1. Kay AB. Allergy and allergic diseases. Second of two parts. N Engl J Med 2001; 344(2): 109-13.
  2. Kay AB. Overview of 'allergy and allergic diseases: with a view to the future'. Br Med Bull 2000; 56(4): 843-64.
  3. Uphoff EP, Cabieses B, Wright J, Pickett KE. International prevalence rates of asthma and allergy are associated with income inequality. J Allergy Clin Immunol 2015; 136(1): 189-90.
  4. Villa-Nova H, Spinola-Castro AM, Garcia FE, Sole D. Prevalence of allergic diseases and/or allergic sensitisation in children and adolescents with type 1 diabetes mellitus. Allergol Immunopathol 2015; 43(2): 157-61.
  5. Arshad SH, Stevens M, Hide DW. The effect of genetic and environmental factors on the prevalence of allergic disorders at the age of two years. Clin Exp Allergy 1993; 23(6): 504-11.
  6. Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 2010; 125(2 Suppl 2): S73-S80.
  7. Romagnani S. The role of lymphocytes in allergic disease. J Allergy Clin Immunol 2000; 105(3): 399-408.
  8. Heufler C, Topar G, Grasseger A, Stanzl U, Koch F, Romani N, et al. Interleukin 7 is produced by murine and human keratinocytes. J Exp Med 1993; 178(3): 1109-14.
  9. Cairns JA, Walls AF. Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J Immunol 1996; 156(1): 275-83.
  10. Yamada N, Wakugawa M, Kuwata S, Nakagawa H, Tamaki K. Changes in eosinophil and leukocyte infiltration and expression of IL-6 and IL-7 messenger RNA in mite allergen patch test reactions in atopic dermatitis. J Allergy Clin Immunol 1996; 98(6 Pt 2): S201-S206.
  11. Barnes PJ. Pathophysiology of allergic inflammation. Immunol Rev 2011; 242(1): 31-50.
  12. Shamim Z, Ryder LP, Heilmann C, Madsen H, Lauersen H, Andersen PK, et al. Genetic polymorphisms in the genes encoding human interleukin-7 receptor-alpha: prognostic significance in allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 37(5): 485-91.
  13. Shamim Z, Müller K, Svejgaard A, Poulsen LK, Bodtger U, Ryder LP. Association between genetic polymorphisms in the human interleukin-7 receptor a-chain and inhalation allergy. Int J Immunogenet 2007; 34(3): 149-53.
  14. Mazzucchelli R, Hixon JA, Spolski R, Chen X, Li WQ, Hall VL, et al. Development of regulatory T cells requires IL-7Ralpha stimulation by IL-7 or TSLP. Blood 2008; 112(8): 3283-92.
  15. Jiang Q, Li WQ, Aiello FB, Mazzucchelli R, Asefa B, Khaled AR, et al. Cell biology of IL-7, a key lymphotrophin. Cytokine Growth Factor Rev 2005; 16(4-5): 513-33.
  16. Goodwin RG, Lupton S, Schmierer A, Hjerrild KJ, Jerzy R, Clevenger W, et al. Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci U S A 1989; 86(1): 302-6.
  17. Seddon B, Tomlinson P, Zamoyska R. Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells. Nat Immunol 2003; 4(7): 680-6.
  18. Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, et al. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet 2007; 39(9): 1083-91.
  19. Tremblay K, Daley D, Chamberland A, Lemire M, Montpetit A, Laviolette M, et al. Genetic variation in immune signaling genes differentially expressed in asthmatic lung tissues. J Allergy Clin Immunol 2008; 122(3): 529-36.
  20. Nachman MW. Single nucleotide polymorphisms and recombination rate in humans. Trends Genet 2001; 17(9): 481-5.
  21. Cierny D, Hanysova S, Michalik J, Kantorova E, Kurca E, Skerenova M, et al. Genetic variants in interleukin 7 receptor alpha chain (IL-7Ra) are associated with multiple sclerosis risk and disability progression in Central European Slovak population. J Neuroimmunol 2015; 282: 80-4.
  22. Lundmark F, Duvefelt K, Iacobaeus E, Kockum I, Wallstrom E, Khademi M, et al. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nat Genet 2007; 39(9): 1108-13.
  23. Hoffjan S, Beygo J, Akkad DA, Parwez Q, Petrasch-Parwez E, Epplen JT. Analysis of variation in the IL7RA and IL2RA genes in atopic dermatitis. J Dermatol Sci 2009; 55(2): 138-40.
  24. Hoffjan S, Epplen JT. The genetics of atopic dermatitis: recent findings and future options. J Mol Med (Berl) 2005; 83(9): 682-92.
  25. Kurz T, Hoffjan S, Hayes MG, Schneider D, Nicolae R, Heinzmann A, et al. Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci. J Allergy Clin Immunol 2006; 118(2): 396-402.
  26. Sinha S, Singh J, Jindal SK. Association of interleukin 7 receptor (rs1494555 and rs6897932) gene polymorphisms with asthma in a north Indian population. Allergy Rhinol (Providence) 2015; 6(3): 168-76.
  27. Fischer A, Hacein-Bey S, Cavazzana-Calvo M. Gene therapy of severe combined immunodeficiencies. Nat Rev Immunol 2002; 2(8): 615-21.
  28. Safaei S, Pourpak Z, Moin M, Houshmand M. IL7R and RAG1/2 Genes Mutations/Polymorphisms in Patients SCID. Iran J Allergy Asthma Immunol 2011; 10(2): 129-32.
  29. Kelly EA, Koziol-White CJ, Clay KJ, Liu LY, Bates ME, Bertics PJ, et al. Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. J Immunol 2009; 182(3): 1404-10.
  30. Kreft KL, Verbraak E, Wierenga-Wolf AF, van Meurs M, Oostra BA, Laman JD, et al. Decreased systemic IL-7 and soluble IL-7Ralpha in multiple sclerosis patients. Genes Immun 2012; 13(7): 587-92.
Journal of Isfahan Medical School
Volume 34, Issue 397 - Serial Number 397
July and August 2016
Pages 1019-1024

Files

History

  • Receive Date: 01 June 2016
  • Revise Date: 06 May 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics