Lack of Association between Toll Like Receptor-2 and Toll Like Receptor-4 Gene Polymorphisms and Other Feature in Iranian Asthmatics Patients
Abstract
Asthma as a chronic inflammatory airway disease is considered to be the most common chronic disease that is involving genetic and environmental factors. Toll like receptors (TLRs) and other inflammatory mediators are important in modulation of inflammation. In this study, we evaluated the role of TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms in the asthma susceptibility, progress, control levels and lung functions in Iranian patients. On 99 asthmatic patients and 120 normal subjects, TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were evaluated by PCR-RFLP method recruiting Msp1 and Nco1 restriction enzymes, respectively. IgE serum levels by ELISA technique were determined and asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. Our results indicated that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between control subjects and asthmatics and were not related to in asthma features such as IgE levels, asthma history and pulmonary factors. Wherease some previous studies indicated TLRs and their polymorphisms might have some role in asthma incidence and features, our data demonstrated that TLR2 Arg753Gln and TLR4 Asp299Gly gene variants were not risk factors for asthma or its features in Iranian patients. Genetic complexity, ethnicity, influence of other genes or polymorphisms may overcome these polymorphisms in our asthmatics.
1. Basehore M J, Howard T D, Lange L A, Moore WC, Hawkins GA, Marshik PL, et al. 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 2004;114(1):80-7.
2. Price D, Thomas M. Thomas, Breaking new ground:challenging existing asthma guidelines. BMC Pulm. Med 2006; 6 (Suppl 1):S6.
3. Georgy V, Fahim HI, El-Gaafary M, Walters S.Prevalence and socioeconomic associations of asthma and allergic rhinitis in northern Africa. Eur Respir J 2006;28(4):756–62.
4. Aoki T, Hirota T, Tamar M, Ichikawa K, Takeda K, Arinami T, et al. An association between asthma and TNF-308G/A polymorphism: meta-analysis. J Hum Genet 2006; 51(8):677-85.
5. Barnes PJ. The role of inflammation and anti- inflammatory medication in asthma. Respir med 2002; 96 (Suppl A):S9-Sl5.
6. Ngoc PL, Gold DR, Tzianabos AO, Weiss ST, Celedon JC. Cytokines, allergy, and asthma. Curr Opin Allergy Clinical immunol 2005; 5(2):161-6.
7. Imler JL, Hoffmann JA. Toll receptors in innate immunity. Trends Cell Biol 2001; 11(7):304-11.
8. O’Neill LA, Bowie AG. The family of fi ve: TIR-domain- containing adaptors in Toll-like receptor signaling. Nat Rev Immunol 2007; 7(5):353-64.
9. Lien E, Sellati TJ, Yoshimura A, Flo TH, Rawadi G, Finberg RW, et al. Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products. J Biol Chem 1999: 33419–25.
10. Sun D, Yang X, Zhao X, Liu E. Alterations in intestinal microflora balance induce maturity and increase the expressions of TLR2 and TLR4 of dendritic cells in mouse lung. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2013; 29(9):923-6.
11. Sutmuller RP, den Brok MH, Kramer M, Bennink EJ, Toonen LW, Kullberg BJ, et al. Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Invest 2006; 116(2):485–94.
12. Gao Z, Dosman JA, Rennie DC, Schwartz DA, Yang IV, Beach J, et al. Association of Toll-like receptor 2 gene polymorphisms with lung function in workers in swine operations. Ann Allergy Asthma Immunol. 2013;110(1):44-50.
13. Brandt EB, Gibson AM, Bass S, Rydyznski C, Khurana Hershey GK. Exacerbation of allergen-induced eczema in TLR4- and TRIF-deficient mice. J Immunol 2013;191(7):3519-25.
14. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2006. [Cited 2007March 21]. Available from: http://www.ginasthma.org.
/>15. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Available from: http://www.asthmacontrol.com.
/>16. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11(5):373-4.
17. Fransson M, Adner M, Erjefalt J, Jansson L, Uddman R, Cardell LO. Upregulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis. Respir Res 2005; 6:100.
18. Yang HZ, Cui B, Liu HZ, Chen ZR, Yan HM, Hua F, et al. Targeting TLR2 attenuates pulmonary inflammation and fibrosis by reversion of suppressive immune microenvironment. J Immunol 2009; 182(1):692-702.
19. Poole JA, Wyatt TA, Kielian T, Oldenburg P, Gleason AM, Bauer A, et al. Toll-like receptor 2 regulates organic dustinduced airway inflammation. Am J Respir Cell Mol Biol 2011; 45(4):711-9.
20. Zhang Q, Qian FH, Zhou LF, Wei GZ, Jin GF, Bai JL, et al. Polymorphisms in toll-like receptor 4 gene are associated with asthma severity but not susceptibility in a Chinese Han population. J Investig Allergol Clin Immunol 2011; 21(5):370-7.
21. Qian FH, Zhang Q, Zhou LF, Jin GF, Bai JL, Yin KS.Polymorphisms in the toll-like receptor 2 subfamily and risk of asthma: a case-control analysis in a Chinese population. J Investig Allergol Clin Immunol 2010;20(4):340-6.
}22. Kerkhof M, Postma DS, Brunekreef B, Reijmerink NE, Wijga AH, de Jongste JC, et al. Toll-like receptor 2 and 4 genes influence susceptibility to adverse effects of traffic- related air pollution on childhood asthma. Thorax 2010;65(8):690-7.
23. Gao Z, Dosman JA, Rennie DC, Schwartz DA, Yang IV, Beach J, et al. Association of Toll-like receptor 2 gene polymorphisms with lung function in workers in swine operations. Ann Allergy Asthma Immunol 2013;110(1):44-50.
24. Smit LA, Bongers SI, Ruven HJ, Rijkers GT, Wouters IM, Heederik D, et al. Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study. Clin Exp Allergy 2007; 37(11):1602-8.
25. Daneshmandi S, Pourfathollah AA, Pourpak Z, Heidarnazhad H, Kalvanagh PA. Cytokine gene polymorphism and asthma susceptibility, progress and control level. Mol Biol Rep 2012; 39(2):1845-53.
| Files | ||
| Issue | Vol 14, No 1 (2015) | |
| Section | Articles | |
| Keywords | ||
| Asthma Polymorphism RFLP-PCR TLR2 TLR4 | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
