Immunity to endotoxin and Asp299Gly polymorphism of TLR-4 in adult patients with early and late onset of asthma


  • Yu. A. Bisyuk
  • A. I. Kurchenko
  • V. E. Kondratiuk
  • A. I. Dubovyi



Bronchial Asthma, Endotoxins, Polymorphism, Genetic


Aim. The gene polymorphism of Asp299Gly TLR-4 may be associated with the risk of asthma development.

Methods and results. The gene polymorphism of TLR-4 (Asp299Gly) receptor has been researched in 262 early-onset and in 69 late-onset asthma patients. The state of anti-endotoxin immunity was assessed by determination of specific antibodies to the endotoxin of A, M, G classes and sCD14 by ELISA. The polymorphism was analyzed by the allele-specific polymerase chain reaction with electrophoretic detection. It was estimated that the risk of early-onset asthma in the population of Crimea is associated with genotypes AG and GG (Asp299Gly) of TLR-4. There were increased levels of anti-endotoxin IgM and decreased of sIgA in patients with late-onset asthma and AA genotype as compared to other genotypes.

Conclusion. The gene polymorphism of Asp299Gly TLR-4 is associated with the risk of early-onset asthma development in Crimea population.


To, T., Stanojevic, S., Moores, G., Gershon, A., Bateman, E., Cruz, A., & Boulet, L. (2012). Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health, 12(1), 204. doi:10.1186/1471-2458-12-204.

Holgate, S. (2012). Innate and adaptive immune responses in asthma. Nat Med, 18(5), 673-683. doi:10.1038/nm.2731.

Lambrecht, B., & Hammad, H. (2014). The immunology of asthma. Nat Immunol, 16(1), 45-56. doi:10.1038/ni.3049.

Kim, Y., Kim, Y., Jeon, S., & Kim, Y. (2013). Immunopathogenesis of Allergic Asthma: More Than the Th2 Hypothesis. Allergy, Asthma & Immunology Research, 5(4), 189. doi:10.4168/aair.2013.5.4.189.

Park, B., & Lee, J. (2013). Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med, 45(12), e66. doi:10.1038/emm.2013.97.

Tesse, R., Pandey, R., & Kabesch, M. (2010). Genetic variations in toll-like receptor pathway genes influence asthma and atopy. Allergy, 66(3), 307-316. doi:10.1111/j.1398-9995.2010.02489.x.

Simpson, A., & Martinez, F. (2010). The role of lipopolysaccharide in the development of atopy in humans. Clinical & Experimental Allergy, 40(2), 209-223. doi:10.1111/j.1365-2222.2009.03391.x.

Yang, I., Barton, S., Rorke, S., Cakebread, J., Keith, T., & Clough, J. et al. (2004). Toll-like receptor 4 polymorphism and severity of atopy in asthmatics. Genes Immun, 5(1), 41-45. doi:10.1038/sj.gene.6364037.

Lundberg, A., Wikberg, L., Ilonen, J., Vaarala, O., & Bottcher, M. (2008). Lipopolysaccharide-Induced Immune Responses in Relation to the TLR4(Asp299Gly) Gene Polymorphism. Clinical And Vaccine Immunology, 15(12), 1878-1883. doi:10.1128/cvi.00241-08.

Yingshui, Y., Xiaohua, R., Lianping, H., Jie, L., Yuelong, J., Weiwei, C., Chaopin, L. (2014). TLR4 +896A>G (Asp299Gly) polymorphism is not associated with asthma: a update meta-analysis. International Journal Of Clinical And Experimental Medicine, 7(12), 5358-5361.

Moore, W., Meyers, D., Wenzel, S., Teague, W., Li, H., & Li, X. et al. (2010). Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med, 181(4), 315-323. doi:10.1164/rccm.200906-0896oc.

Gordienko, A. I., Biloglazov, V. O. Patent 70193 A Ukrayina MKI 7 A61K31/01 Sposib viznachennya antitil do lipolisaharidiv gram negativnih bakteriy; Zavl. 29.12.2003; Opubl. 15.09.2004, Byul. # 9 [in Ukraine].

Gordienko, A.I. (2009). Ispolzovanie tverdofaznogo immunofermentnogo analiza dlya opredeleniya obschego i antiendotoksinovogo sekretornogo IgA cheloveka [The use of ELISA for the determination of total and anti-endotoxin human secretory IgA]. Tavricheskiy mediko-biologicheskiy vestnik. 12(3), 82-89. [in Ukraine].

Sackesen, C., Karaaslan, C., Keskin, O., Tokol, N., Tahan, F., & Civelek, E. et al. (2005). The effect of polymorphisms at the CD14 promoter and the TLR4 gene on asthma phenotypes in Turkish children with asthma. Allergy, 60(12), 1485-1492. doi:10.1111/j.1398-9995.2005.00874.x.

Hussein, Y., Awad, H., Shalaby, S., Ali, A., & Alzahrani, S. (2012). Toll-like receptor 2 and Toll-like receptor 4 polymorphisms and susceptibility to asthma and allergic rhinitis: A case-control analysis. Cellular Immunology, 274(1-2), 34-38. doi:10.1016/j.cellimm.2012.02.006.

How to Cite

Bisyuk YA, Kurchenko AI, Kondratiuk VE, Dubovyi AI. Immunity to endotoxin and Asp299Gly polymorphism of TLR-4 in adult patients with early and late onset of asthma. Zaporozhye Medical Journal [Internet]. 2015Jun.15 [cited 2024Jul.20];17(3). Available from:



Original research