Association of Toll-like receptors 4 (TLR-4) gene expression and polymorphisms in patients with severe asthma

Abstract

Innate immunity plays a central role in the pathogenesis of severe asthma, and it is closely linked to elevated IgE and Toll-like receptor 4 (TLR-4) levels. However, there is a scarcity of information about the association of the TLR-4 receptor polymorphism in the pathogenesis of severe asthma. This study highlights the level of gene expression of different alleles in asthmatic patients compared to healthy control individuals. This was a randomized control trial, which included 150 patients with asthma (with high serum levels of IgE) with a matching 150 healthy control individuals. Participants had a series of blood tests to measure various immune parameters: interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), intercellular adhesion molecule-1 (ICAM1) and detect allele type and gene expression of the TLR-4 gene. Patients with asthma had significantly higher levels of IL-8 when compared to the healthy control participants. In addition, in the rs91 genotyping, there were significant differences in the levels of IL-8 and TNF between CC and TT genotyping. While in rs90 TLR-4, TNF levels were significantly higher in AA vs. AG and GG genotypes among the asthmatic patients when compared to the control group. The results showed that in TLR-4, rs4986791 were significantly associated with asthma risk. Polymorphisms in TLRs play essential roles in asthma.

Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis

“…TLR4/MyD88/NF-κB signaling pathway leads to the increase of downstream pro-inflammatory cytokines and adhesion molecules, participate in the occurrence of inflammatory reactions [ 31 ], and cause the pathological changes such as vascular extravasation or increased vascular permeability, vascular obstruction, and degeneration and pathological changes of neovascularization, thus leading to the occurrence and development of DMI [ 32 , 33 ]. Activation of the TLR4 signaling pathway mediates the inflammatory response, which is associated with TLR4 gene polymorphism [ 34 ]. Genetic variation of TLR4 can alter TLR4’s recognition and interaction functions, and then, change the immune response [ 9 ].…”

Gene polymorphisms in asthma: a narrative review

“…These findings are important for the early diagnosis and prevention of asthma, as well as for the development of treatment strategies for this chronic inflammatory disease. The results of another meta-analysis indicate that rs3804099 in TLR2 and rs4986791 in TLR4 are significantly associated with the risk of asthma (32,33). Tizaoui et al (34) found that the TLR9-1237 polymorphism was weakly correlated with the risk of asthma in a codominant model, while an analysis using an allele comparison model indicated that the major TLR9-1237 T alleles were often important protective factors.…”