Association between Interleukin-23 Receptor R381Q Gene Polymorphism and Asthma
-
Ali Mosayebian
,
Mazdak Ganjalikhani-Hakemi
,
Rezvan Meshkat
,
Ramin Ghasemi
,
Hossain Khan-Ahmad
,
Morteza Samadi
Abstract
The SNP (rs11209026, Arg381Gln, R381Q) in the IL-23 receptor (IL23R) confers protection against multiple inflammatory diseases, representing one of the most significant human genetic polymorphisms in inflammatory diseases. We, therefore, investigated the association between IL-23 R R381Q gene polymorphism and asthma.This case-control study was performed on 209 patients, and 200 healthy controls. Using PCR-RFLP, the R381Q variant was screened in the IL-23R gene of the patients and controls.Serum IgE levels were measured using ELISA technique. Eosinophil absolute count was done with Sesmex cell counter.Our results indicated that the genotype and allele frequencies of the IL-23R R381Q polymorphism is significantly different between asthmatic patients and control subjects (p<0.001; odd ratio= 0.266; 95%, CI=0.118-0.604. Moreover, the asthmatic patients had higher eosinophil count and total serum IgE levels than controls as expected (p<0.001).The present study suggested that R381Q polymorphism in IL-23 receptor may be a predisposing allele for asthma.
1. Hellings PW KA, Liu Z, Vandekerckhove P, Wuyts A, Overbergh L, et al. Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol 2003; 28(1):42-50.
2. Oda N, Canelos PB, Essayan DM, Plunkett BA, Myers AC, Huang SK. Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response. Am J Respir Crit Care Med 2005; 171(1):12-8.
3. Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Pagé N, et al. IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001; 108(3):430-8.
4. Jatakanon A UC, Maziak W, Lim S, Chung KF, Barnes PJ.Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 1999; 160(5 Pt 1):1532-9.
5. Louis R LL, Bron AO, Roldaan AC, Radermecker M, Djukanovi ćR. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med 2000; 161(1):9-16.
6. Oppmann B LR, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13(5):715-25.
7. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road Immunity 2008; 28(4):445-53.
8. Korn T BE, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol 2009; 27:485-517.
9. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201(2):233-40.
10. Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce- Shaikh B, Stepankova R, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 2006; 25(2):309–18.
11. Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ,McKenzie BS, et al. Interleukin- 23 drives innate and Tcell-mediated intestinal inflammation. J Exp Med 2006;203(11):2473–83.
12. Ahern PP, Schiering C, Buonocore S, McGeachy MJ, Cua DJ, Maloy KJ, et al. Interleukin-23 drives intestinal inflammation through direct activity on T cells Immunity 2010; 33(2):279–88.
13. Wakashin H, Hirose K, Maezawa Y, Kagami S, Suto A, Watanabe N, et al. IL-23 and Th17 cells enhance Th2- cell-mediated eosinophilic airway inflammation in mice. Am J Respir Crit Care Med 2008; 178(10):1023-32.
14. Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 2002;168(11):5699–708.
15. Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 Receptor ( IL-23R ) Gene Protects Against Pediatric Crohn’s Disease. Inflamm Bowel Dis 2007; 13(5):511–5.
16. Guan Q1, Ma Y, Aboud L, Weiss CR, Qing G, Warrington RJ, et al. Targeting IL-23 by employing a p40 peptide-based vaccine ameliorates murine allergic skin and airway inflammation. Clin Exp Allergy 2012;42(9):1397–405.
17. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314(5804):1461-3.
18. Capon F, Di Meglio P, Szaub J, Prescott NJ, Dunster C, Baumber L, et al. Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B)confer protection against psoriasis. Hum Genet 2007;122(2):201-6.
19. Rueda B, Orozco G, Raya E, Fernandez-Sueiro JL, Mulero J, Blanco FJ, et al. The IL23R Arg381Gln non- synonymous polymorphism confers susceptibility to ankylosing spondylitis. Ann RheumDis 2008;67(10):1451-4.
20. Wu Q, Hu L, Cai P, Li Y, Chen F, Kong L. Association Analysis of TIM-1-232 G> A and 5383-5397Insertion/Deletion Polymorphisms With Childhood Asthma and Total Serum Immunoglobulin E Levels in Middle China. J Investig Allergol Clin Immunol 2009;19(2):146-53.
21. Mark fitz gerald EDB, Louis philippe Boulet. Global Initiative for Asthma: GINA Publications; 2012. Available from: http://www.ginasthma.org.
22. Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F.Th17 cells: new players in asthma pathogenesis. Allergy 2011; 66(8):989–98.
23. Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev 2008, 226):55-79.
24. McGeachy MJ, Chen Y, Tato CM, Laurence A, Joyce- Shaikh B, Blumenschein WM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 2009; 10(3):314–24.
25. Di Meglio P, Di Cesare A, Laggner U, Chu CC, Napolitano L, Villanova F, et al. The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans. PLoS ONE 2011; 6(2):e17160.
26. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene. SCIENCE 2007; 314(5804):1461-3.
27. Nestle FO, Kaplan DH, Barker J. N Engl J Med 2009;361(5):496–509.
28. Di Meglio P, Di Cesare A, Laggner U, Chu CC, Napolitano L, Villanova F, et al. The IL23R R381Q Gene Variant Protects against Immune-Mediated Diseases by Impairing IL-23-Induced Th17 Effector Response in Humans. PLoS ONE 2011; 6(2):e1716.
29. Lakatos PL, Szamosi T, Szilvasi A, Molnar E, Lakatos L, Kovacs A, et al. ATG16L1 and IL23 receptor (IL23R) genes are associated with disease susceptibility in Hungarian CD patients Dig Liver Dis 2008; 40(11):867–73.
| Files | ||
| Issue | Vol 14, No 4 (2015) | |
| Section | Original Article(s) | |
| Keywords | ||
| Asthma IL-23 Receptor Single Nucleotide Polymorphism | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
