IL-13 Gene Polymorphisms and Their Association with Atopic Asthma and Rhinitis in Pakistani Patients
Abstract
Interleukin-13 (IL-13) is known to be a key regulator in immunoglobulin E (IgE) synthesis, mucus hypersecretion and airway hyperresponsiveness. Single nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations.This study was performed in 214 atopic patients (asthma n=108, allergic rhinitis n=106) and sex-matched healthy controls (n=120). Genotyping of IL-13 gene polymorphisms was performed using polymerase chain reaction-based restriction fragment length polymorphism method.A statistically significant association of the A-1512C polymorphism in IL13 gene was observed with atopy (p<0.001; χ2=19.0). Upon stratification of the data into asthma and AR association was revealed with both asthma (p=0.01; χ2=8.80) and AR (p<0.001; χ2=24.3) in Pakistani patients. Higher odds ratio (OR 95% CI) was observed for AR 3.42 (2.04-5.76) relative to asthma 2.40 (1.41-4.09) for the C allele compared to controls.In conclusion the study provides the evidence A-1512C polymorphisms in IL-13 is a risk factor for asthma and AR.
1. Prieto J, Lensmar C, Roquet A, van der Ploeg I, Gigliotti D, Eklund A, et al. Increased interleukin-13 mRNA expression in bronchoalveolar lavage cells of atopic patients with mild asthma after repeated low dose allergen provocations. Respir Med 2000; 94(8):806-14.
2. Bodey KJ, Semper AE, Redington AE, Madden J, Teran LM, Holgate ST, et al. Cytokine profiles of BALT cells and T-cell clones obtained from human asthmatic airways after local allergen challenge. Allergy 1999; 54(10):1083-93.
3. Truyen E, Coteur L, Dilissen E, Overbergh L, Dupont LJ, Ceuppens JL, et al. Evaluation of airway inflammation by quantitative Th1/Th2 cytokine mRNA measurement in sputum of asthma patients. Thorax 2006; 61(3):202-8.
4. Park SW, Jangm HK, An MH, Min JW, Jang AS, Lee JH, et al. Interleukin- 13 and interleukin-5 in induced sputum of eosinophilic bronchitis: comparison with asthma. Chest 2005; 128(4):1921-7.
5. Pawankar RU, Okuda M, Hasegawa S, Suzuki K, Yssel H, Okubo K, et al. Interleukin-13 expression in the nasal mucosa of perennial allergic rhinitis. Am J Respir Crit Care Med 1995; 152(6 Pt 1):2059-67.
6. Ghaffar O, Laberge S, Jacobson MR, Lowhagen O, Rak S, Durham SR, et al. IL-13 mRNA and immunoreactivity in allergen-induced rhinitis: comparison with IL-4 expression and modulation by topical glucocorticoid therapy. Am J Respir Cell Mol Biol 1997; 17(1):17-24.
7. McKenzie GJ, Bancroft A, Grencis RK, McKenzie AN.A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Curr Biol 1998; 8(6):339-42.
8. Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998; 282(5397):2261-3.
9. Miyahara S, Miyahara N, Matsubara S, Takeda K, Koya T, Gelfand EW. IL-13 is essential to the late-phase response in allergic rhinitis. J Allergy Clin Immunol 2006; 118(5):1110-6.
10. Heinzmann A, Mao XQ, Akaiwa M, Kreomer RT, Gao PS, Ohshima K, et al. Genetic variants of IL-13 signalling and human asthma and atopy. Hum Mol Genet 2000;9(4):549-59.
11. Bottema RWB, Nolte IM, Howard TD, Koppelman GH, Dubois AEJ, de Meer G, et al. Interleukin 13 and Interleukin 4 Receptor- Polymorphisms in Rhinitis and Asthma. Int Arch Allergy Immunol 2010; 153(3):259-67.
12. Graves PE, Kabesch M, Halonen M, Holberg CJ, Baldini M, Fritzsch C, et al. A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J Allergy Clin Immunol 2000; 105(3):506-13.
13. Yang H, Dong H, Dai Y, Zheng Y. Association of interleukin-13 C-1112T and G+2044A polymorphisms with asthma: ameta-analysis. Respirology 2011;16(7):1127-35.
14. Vladich FD, Brazille SM, Stern D, Peck ML, Ghittoni R, Vercelli D. IL-13 R130Q, a common variant associated with allergy and asthma, enhances effector mechanisms essential for human allergic inflammation. J Clin Invest 2005; 115(3):747-54.
15. Bunyavanich S, Shargorodsky J, Celedón JC. A meta- analysis of Th2 pathway genetic variants and risk for allergic rhinitis. Pediatr Allergy Immunol 2011;22(4):378-87.
16. Micheal S, Minhas K, Ishaque M, Ahmed F, Ahmed A.Promoter polymorphisms of the CD14 gene are associated with atopy in Pakistani adults. J Investig Allergol Clin Immunol 2011; 21(5):394-7.
17. Sambrook J, Russell DW, Sambrook J. The condensed protocols from Molecular cloning: a laboratory manual. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2006.
18. Maier LM, Howson JM, Walker N, Spickett GP, Jones RW, Ring SM, et al. Association of IL13 with total IgE: evidence against an inverse association of atopy and diabetes. J Allergy Clin Immunol 2006; 117(6):1306-13.
19. Humbert M, Durham SR, Kimmitt P, Powell N, Assoufi B, Pfister R, t al. Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J Allergy Clin Immunol 1997; 99(5):657-65.
20. Huang SK, Xiao HQ, Kleine-Tebbe J, Paciotti G, Marsh DG, Lichtenstein LM, et al. IL-13 expression at the sites of allergen challenge in patients with asthma. J Immunol 1995; 155(5):2688-94.
21. Akdis M, Akdis CA, Weigl L, Disch R, Blaser K. Skin- homing, CLA_ memory T cells are activated in atopic dermatitis and regulate IgE by an IL-13-dominated cytokine pattern: IgG4 counter-regulation by CLA- memory T cells. J Immunol 1997; 159(9):4611-9.
22. Katagiri K, Itami S, Hatano Y, Takayasu S. Increased levels of IL-13 mRNA, but not IL-4 mRNA, are found in vivo in peripheral blood mononuclear cells (PBMC) of patients with atopic dermatitis (AD). Clin Exp Immunol 1997; 108(2):289-94.
23. Emson CL, Bell SE, Jones A, Wisden W, McKenzie AN.Interleukin (IL)-4-independent induction of immunoglobulin (Ig)E, and perturbation of T cell development in transgenic mice expressing IL-13. J Exp Med 1998; 188(2):399-404.
24. Zurawski G, de Vries JE. Interleukin-13, an interleukin-4 like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 1994; 15(1):19-26.
25. Horie S, Okubo Y, Hossain M, Sato E, Nomura H, Koyama S, et al. Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis. Intern Med 1997; 36(3):179-85.
26. Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science 1998; 282(5397):2258-61.
27. Danahay H, Atherton H, Jones G, Bridges RJ, Poll CT.Interleukin- 13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 2002; 282(2):L226-36.
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Issue | Vol 12, No 4 (2013) | |
Section | Articles | |
Keywords | ||
Allergic rhinitis(AR) Atopic asthma Interleukin-13 (IL-13) Polymorphism |
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