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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.

SUBMITTER: Shukur W

PROVIDER: S-EPMC8485369 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria.

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| S-EPMC1324982 | biostudies-literature

Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease.

Project description:Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions of certain key TLR-related signaling pathways, which subsequently increases the risk of autoimmune diseases. We illustrate and discuss the current findings on the role of Toll-like receptor gene polymorphisms in numerous autoimmune diseases in this review, such as type 1 diabetes mellitus, Graves' disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. The study of genetic variation in TLRs in different populations has shown a complex interaction between immunity and environmental factors. This interaction suggests that TLR polymorphisms affect the susceptibility to autoimmune diseases differently in various populations. The identification of Toll-like receptor gene polymorphisms can expand our understanding of the pathogenesis of autoimmune diseases, which will subsequently guide effective medical management and provide insight into prognosis and advanced treatments.

| S-EPMC8107678 | biostudies-literature

Polymorphisms of toll like receptors in the genetics of severe RSV associated diseases.

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| S-EPMC3827794 | biostudies-other

Toll-Like Receptor 2 (TLR-2) Gene Polymorphisms in Type 2 Diabetes Mellitus.

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| S-EPMC6099132 | biostudies-literature

Polymorphisms at Locus 4p14 of Toll-Like Receptors TLR-1 and TLR-10 Confer Susceptibility to Gastric Carcinoma in Helicobacter pylori Infection.

Project description:Helicobacter pylori (H. pylori) -induced gastric inflammation impacts the functions of leptin- and ghrelin-producing cells in the gastroduodenum. Inflammation resulting from H. pylori sensing via Toll-like receptors (TLRs) and the associated downstream signaling largely remain ambiguous. Here, we investigated the role of gut hormones, pro-inflammatory cytokines and single nucleotide polymorphisms (SNPs) associated with TLR 4p14 in H. pylori disease in 30 subjects with non-ulcer dyspepsia (NUD), 40 with peptic ulcer disease (PUD) and 15 with gastric cancer (GC) subjects positive and negative for H. pylori infection. The level of pro-inflammatory cytokines was directly proportional to the severity of gastritis, and disease status influenced the levels of gut hormones and pro-inflammatory cytokines. TLR-1 SNPs rs4833095 and TLR-10 SNPs rs10004195 and were directly associated with H. pylori disease, and were up-regulated in the presence of H. pylori in a genotype-independent manner. We concluded that TLR-1 rs4833095 and TLR10 rs10004195 confer susceptibility to development of gastroduodenal disease, especially GC in H.pylori disease.

| S-EPMC4641589 | biostudies-literature

Structure of fish Toll-like receptors (TLR) and NOD-like receptors (NLR).

Project description:Innate immunity driven by pattern recognition receptor (PRR) protects the host from invading pathogens. Aquatic animals like fish where the adaptive immunity is poorly developed majorly rely on their innate immunity modulated by PRRs like toll-like receptors (TLR) and NOD-like receptors (NLR). However, current development to improve the fish immunity via TLR/NLR signaling is affected by a poor understanding of its mechanistic and structural features. This review discusses the structure of fish TLRs/NLRs and its interaction with pathogen associated molecular patterns (PAMPs) and downstream signaling molecules. Over the past one decade, significant progress has been done in studying the structure of TLRs/NLRs in higher eukaryotes; however, structural studies on fish innate immune receptors are undermined. Several novel TLR genes are identified in fish that are absent in higher eukaryotes, but the function is still poorly understood. Unlike the fundamental progress achieved in developing antagonist/agonist to modulate human innate immunity, analogous studies in fish are nearly lacking due to structural inadequacy. This underlies the importance of exploring the structural and mechanistic details of fish TLRs/NLRs at an atomic and molecular level. This review outlined the mechanistic and structural basis of fish TLR and NLR activation.

| S-EPMC7396143 | biostudies-literature

Association of single-nucleotide polymorphisms in toll-like receptor 2 gene with asthma susceptibility: A meta-analysis.

Project description:BackgroundAn increasing number of studies have been carried out on the relationship between polymorphisms in toll-like receptor 2 (TLR2) gene and asthma risk. However, the results were controversial. With the purpose of yielding a more reliable estimation of the association, we conducted the present meta-analysis.MethodsMultiple electronic databases up to August 22, 2016 were searched for literature retrieval. The association between the asthma susceptibility and the rs5743708 polymorphism, rs3804099 polymorphism, rs3804100 polymorphism, and rs4696480 polymorphism in TLR2 gene was appraised. The odds ratios (ORs) with 95% confidence intervals (CIs) under different genetic models were calculated.ResultsA total of 13 studies were eligible in our meta-analysis according to the predefined inclusion and exclusion criteria. There was no significant association between asthma risk and rs5743708, rs3804099, and rs3804100 polymorphisms in TLR2 gene under any genetic model. With respect to the TLR2 rs4696480 polymorphism, significant association was detected between asthma susceptibility and TLR2 rs4696480 polymorphism under dominant model (OR = 2.455, 95% CI = 1.235-4.88, P = .01) and codominant 3 model (OR = 2.776, 95% CI = 1.199-6.427, = 0.017).ConclusionsOur meta-analysis reveals that the TLR2 rs4696480 polymorphism is significantly associated with asthma susceptibility, and the TLR2 rs4696480 polymorphism is a risk factor for asthma.

| S-EPMC5440134 | biostudies-literature

Association of cytokine and Toll-like receptor gene polymorphisms with severe malaria in three regions of Cameroon.

Project description:P. falciparum malaria is one of the most widespread and deadliest infectious diseases in children under five years in endemic areas. The disease has been a strong force for evolutionary selection in the human genome, and uncovering the critical human genetic factors that confer resistance to the disease would provide clues to the molecular basis of protective immunity that would be invaluable for vaccine development. We investigated the effect of single nucleotide polymorphisms (SNPs) on malaria pathology in a case- control study of 1862 individuals from two major ethnic groups in three regions with intense perennial P. falciparum transmission in Cameroon. Twenty nine polymorphisms in cytokine and toll-like receptor (TLR) genes as well as the sickle cell trait (HbS) were assayed on the Sequenom iPLEX platform. Our results confirm the known protective effect of HbS against severe malaria and also reveal a protective effect of SNPs in interleukin-10 (IL10) cerebral malaria and hyperpyrexia. Furthermore, IL17RE rs708567 GA and hHbS rs334 AT individuals were associated with protection from uncomplicated malaria and anaemia respectively in this study. Meanwhile, individuals with the hHbS rs334 TT, IL10 rs3024500 AA, and IL17RD rs6780995 GA genotypes were more susceptible to severe malarial anaemia, cerebral malaria, and hyperpyrexia respectively. Taken together, our results suggest that polymorphisms in some immune response genes may have important implications for the susceptibility to severe malaria in Cameroonians. Moreover using uncomplicated malaria may allow us to identify novel pathways in the early development of the disease.

| S-EPMC3842328 | biostudies-literature

Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk.

Project description:BACKGROUND: Endometrial cancer is the most common gynaecological malignancy in women of developed countries. Many risk factors implicated in endometrial cancer trigger inflammatory events; therefore, alterations in immune response may predispose an individual to disease. Toll-like receptors (TLRs) and nucleosome-binding oligomerization domain (NOD) genes are integral to the recognition of pathogens and are highly polymorphic. For these reasons, the aim of the study was to assess the frequency of polymorphic variants in TLR and NOD genes in an Australian endometrial cancer population. METHODS: Ten polymorphisms were genotyped in 191 endometrial cancer cases and 291 controls using real-time PCR: NOD1 (rs2075822, rs2907749, rs2907748), NOD2 (rs5743260, rs2066844, rs2066845), TLR2 (rs5743708), TLR4 (rs4986790) and TLR9 (rs5743836, rs187084). RESULTS: Haplotype analysis revealed that the combination of the variant alleles of the two TLR9 polymorphisms, rs5743836 and rs187084, were protective for endometrial cancer risk: OR 0.11, 95% CI (0.03-0.44), p = 0.002. This result remained highly significant after adjustment for endometrial cancer risk factors and Bonferroni correction for multiple testing. There were no other associations observed for the other polymorphisms in TLR2, TLR4, NOD1 and NOD2. CONCLUSIONS: The variant 'C' allele of rs5743836 causes greater TLR9 transcriptional activity compared to the 'T' allele, therefore, higher TLR9 activity may be related to efficient removal of microbial pathogens within the endometrium. Clearly, the association of these TLR9 polymorphisms and endometrial cancer risk must be further examined in an independent population. The results point towards the importance of examining immune response in endometrial tumourigenesis to understand new pathways that may be implicated in disease.

| S-EPMC2918576 | biostudies-literature

[Association between IL1R1 gene polymorphisms and childhood asthma].

Project description:OBJECTIVE:To investigate the association of two single-nucleotide polymorphisms (SNPs) in IL1R1 gene (rs1558641 and rs949963) with the susceptibility to asthma in children from Central China. METHODS:A case-control study was performed in the asthma group and the control group, consisting of 208 children with asthma and 223 normal children from Central China, respectively. The genotypes of two SNPs in IL1R1 gene, rs1558641 and rs949963, were identified using polymerase chain reaction-restriction fragment length polymorphism. The serum level of IL1R1 was determined by enzyme-linked immunosorbent assay. RESULTS:There were no significant differences in genotype and allele frequencies of rs1558641 between the asthma and control groups. In terms of rs949963, the frequencies of GG genotype and alleles were significantly higher in the asthma group than in the control group (P<0.05). The asthma group had a significantly higher serum level of IL1R1 than the control group (P=0.011). Moreover, the serum level of IL1R1 was significantly higher in patients with GG genotype than in those with AA or AG genotype for rs949963 (P=0.028). CONCLUSIONS:IL1R1 SNP rs949963 is associated with the susceptibility to asthma in children from Central China and may increase the serum expression of IL1R1.

| S-EPMC7389989 | biostudies-literature

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