Toll-like Receptor 4 Polymorphisms Research Articles

Role of rs5743708 SNP in the risk of Bacterial Respiratory Infections in Children of Ramadi city/Iraq

Background and Aim: Respiratory Infections are a major global health and financial burden, so among cause the five most common and deadly for respiratory illnesses is acute lower respiratory tract infections (RTIs), these infections claim over 4 million lives annually. Toll-like receptors (TLRs) are key components of the innate immune system that recognize pathogen which associated a molecular patterns) PAMPs) and initiate an immune response. Understanding the role of TLR polymorphisms in susceptibility to respiratory infections in children is important for developing strategies to prevent and treat these infections. So, the current study aims to "Investigate the potential association between TLR2 gene polymorphisms and susceptibility to respiratory infections in children". Methodology: The study included collect of 300 samples with respiratory infection from both sex with range ages(1-12) years, and other 50 healthy control samples. The samples were collected from general and private hospitals in Ramadi city, Iraq. PCR was carried out using primer for gene target and amplification of target gene. Sanger Sequencing conducted with both direction for all samples. Results and Conclusion: The result of sputum culture indicate that 100 of suspected samples were positive culturing while other demonstrate a negative growth. The results analysis of sequencing according to Query and subjected samples indicated that 4 of patient have SNP of rs5743708 G>A, while there is not found in control samples, and the results of genotype frequencies analysis it was found that TLR2 polymorphism was associated with increased risk for bacterial respiratory infections in children according to under study samples, but no statistical significant differences correlation of rs5743708 G>A and infection, with adjusted odds ratio [OD:5.3; 95%Cl: 0.3-101; P: 0.2].

Toll-Like Receptor Genes and Risk of Latent Tuberculosis Infection in People Infected with HIV-1.

The purpose of this study was to determine the contribution of genetic factors, i.e., the level of expression and polymorphisms of Toll-like receptors (TLR), to the susceptibility of latent tuberculosis infection in a Russian cohort of individuals infected with HIV. The patients (n = 317) with confirmed HIV infection were divided into two groups according to the results of the STANDARD E TB-Feron test: 63 cases with a latent TB infection and 274 controls without LTBI. Total DNA and RNA were isolated from whole-blood samples. SNP genotyping and expression levels of five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR8) were determined by means of real-time PCR. There were no significant differences in the expression levels of the TLRs between the case and control groups. In addition, we did not observe any significant association between the analyzed SNPs and the susceptibility of Latent tuberculosis infection (LTBI) in patients with HIV. However, patients from an entire cohort with the rs4986790-GG (TLR4) and rs5743708-GG (TLR2) genotypes were characterized by lower CD4 T-cell counts compared to carriers of alternative alleles. Moreover, we found a significant risk of a hazardous drop in the CD4 T-cell count below 350 cells/mm3 associated with the rs4986790-G (TLR4) allele. Latent tuberculosis infection in individuals infected with HIV does not significantly modify the level of TLR gene expression.

Genetic association and functional implications of TLR4 rs1927914 polymorphism on colon cancer risk

BackgroundColon cancer remains a major health concern worldwide, with genetic factors playing a crucial role in its development. Toll-like receptors (TLRs) has been implicated in various cancers, but their role in colon cancer is not well understood. This study aims to identify functional polymorphisms in the promoter and 3′UTR regions of TLRs and evaluate their association with colon cancer susceptibility.MethodsWe conducted a case-control study involving 410 colon cancer patients and 410 healthy controls from the Chinese population. Genotyping of polymorphisms in TLR3, TLR4, TLR5 and TLR7 was performed using PCR-RFLP and TaqMan MGB probes. Using logistic regression analysis, we evaluated the association of TLRs polymorphisms and the susceptibility to colon cancer. To understand the biological implications of the TLR4 rs1927914 polymorphism, we conducted functional assays, including luciferase reporter assay and electrophoretic mobility shift assay (EMSA).ResultsOur results demonstrated that the G-allele of the TLR4 rs1927914 polymorphism is significantly associated with a decreased risk of colon cancer (OR = 0.68, 95%CI = 0.50–0.91). Stratified analysis showed that TLR4 rs1927914 AG or GG genotype contributed to a decreased risk of colon cancer among younger individuals (OR = 0.52, 95%CI = 0.34–0.81), males (OR = 0.58, 95%CI = 0.38–0.87), non-smokers (OR = 0.58, 95%CI = 0.41–0.83) and non-drinker with OR (95%CI) of 0.66 (0.46–0.93). Functional assays demonstrated that in HCT116 and LOVO colon cancer cells, the luciferase activity driven by the TLR4 promoter with the rs1927914A allele was 5.43 and 2.07 times higher, respectively, compared to that driven by the promoter containing the rs1927914G allele. Electrophoretic mobility shift assay (EMSA) results indicated that the rs1927914G allele enhanced transcription factor binding. Using the transcription factor prediction tool, we found that the G allele facilitates binding of the repressive transcription factor Oct1, while the A allele does not.ConclusionThe TLR4 rs1927914 polymorphism influence the susceptibility to colon cancer, with the G allele offering a protective effect through modulation of gene expression. These insights enhance our understanding of the genetic determinants of colon cancer risk and highlight TLR4 as a promising target for cancer prevention strategies.

Study of gene polymorphisms in Toll-like receptor 2 in patients with acute lymphoblastic leukemia

ObjectivesAcute Lymphoblastic Leukemia (ALL) is a multifactorial disease that results from the interaction between multiple genetic factors. ALL is characterized by uncontrolled production of hematopoietic precursor cells of the lymphoid progenitors within the bone marrow. The development of hematological malignancies has been associated with malignant-like cells that express low levels of immunogenic surface molecules, thus, facilitating their escape from cellular antineoplastic immune responses. This risk may be partly influenced by variations in polymorphic genes that control immune function and regulation. Toll-like receptors (TLRs) are well known pattern recognition receptors playing key role in innate immune response. Abnormal expression and dysregulation of TLRs will provide an opportunity for cancer cells to escape from the immune system and enhance their proliferation and angiogenesis. Toll-like receptor 2 (TLR2) play an essential role in innate immunity. Single nucleotide polymorphisms (SNPs) are present in a number of TLR genes and have been associated with various disorders. MethodsIn this study, 265 subjects have been divided into two groups included 150 patients with ALL and115 healthy volunteers. All subjects were genotyped using TaqMan PCR techniques. In total, Five SNPs were statistically evaluated in the TLR2 (rs1898830 A/G, rs3804099 T/C, rs3804100 T/C, rs1339 T/C, and rs1337 C/G), which may influence the susceptibility of ALL. Minor allele frequency and genotype distribution were compared across the study groups, and the relative risk and differences between patients and controls were estimated. Moreover, the mRNA expression level was evaluated in patients with ALL and the matched healthy individuals by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). ResultsTLR2 rs1898830 A/G; rs3804099 T/C; rs3804100 T/C; rs1339 T/C, were significantly decrease the risk in our population, overall and for certain subtypes and ALL samples exhibited significant increase in the mRNA levels of TLR2. ConclusionsThis study shows that TLR2 could be an independent prognostic factor of ALL risks in the Saudi population. Suggesting that genetic variation in genes associated with an immune response may be important in the etiology of ALL. In addition, the results herein revealed that TLR2 overexpression is associated with ALL and has diverse biological significance in the context of the complex relationship between inflammation and cancer development. Therefore, these data could open further studies to explore the possible clinical relevance of TLRs as pathological markers for Leukemia and enhance the strategies regarding hematological malignancies prevention based on their gene expression.

The role of Toll-like receptor polymorphism in pathogenesis of cytomegalovirus infection

The role of Toll-like receptor polymorphism in pathogenesis of cytomegalovirus infection

Gene polymorphisms in toll like receptors (TLRS) and susceptibility to recurrent vulvovaginal candidiasis

Gene polymorphisms in toll like receptors (TLRS) and susceptibility to recurrent vulvovaginal candidiasis

Genetic predictors of the risk of developing complications in the immediate postoperative period following combat trauma

Introduction. Paratraumatic eczema (PTE), being a type of microbial eczema, occurs after surgical interventions, chronic wound healing, accompanied by pronounced inflammatory changes with hyperemia, edema, exudation, soreness and itching. Genetic polymorphisms of cytokines and Toll-like receptors (TLRs) may be pathogenetic factors in the development of PTE, causing the penetration of microorganisms and violation of the protective properties of the skin barrier. Goal. To study the relationship of polymorphisms rs1800629 of the TNFα gene, rs5743708 of the TLR2 gene, rs3775291 of the TLR3 gene, rs4986790 of the TLR4 gene with the development of paratraumatic eczema in combat trauma victims. Material and methods. The study included 162 patients, of whom 82 showed signs of PTE (comparison group), 80 people had no signs of PTE (control group). Genotyping of polymorphisms was carried out using the polymerase chain reaction method with electrophoretic detection using test systems of NPF Litech (Russia). The Statistica 10 program (StatSoft, Inc., USA) was used for statistical data processing. Results. A connection with the development of PTE with variants of genotypes and alleles of polymorphisms was established: rs1800629 of the TNFα gene (χ2=6.9; p=0.033 and χ2=8.12; p=0.005); rs3775291 of the TLR3 gene (χ2=6.9; p=0.039 and χ2=5.74; p=0.018); rs4986790 of the TLR4 gene (χ2=8.17; p=0.018 and χ2=7.85; p=0.005). The increase in the chances of developing PTE was influenced by: genotypes GA (OR=1.64; 95% CI 0.83–3.24) and AA (OR=2.94; 95% CI 0.9–9.67), allele A (OR=2.13; 95% CI 1.26–3.6) rs1800629 TNFα gene; genotypes CT (OR=1.58; 74% CI 0.93–3.24) and TT (OR=1.79; 95% CI 0.67–4.8), allele T (OR=1.76; 95% CI 1.1–2.8) rs3775291 TLR3 gene; genotypes AG (OR=2.58; 95% CI 1.24–5.37) and GG (OR=3.0; 95% CI 0.31–29.47), allele G (OR=2.44; 95% CI 1.29–4.62) rs4986790 of the TLR4 gene. Conclusions. Polymorphisms rs1800629 of the TNFα gene, rs3775291 of the TLR3 gene, rs4986790 of the TLR4 gene are associated with the development of paratraumatic eczema in combat trauma victims

Associations of toll-like receptor polymorphisms with systemic lupus erythematosus: A meta-analysis

ObjectiveThe objective of this study was to examine whether polymorphisms in toll-like receptors 7 and 4 (TLR7 and 4) contribute to vulnerability to systemic lupus erythematosus (SLE). MethodsWe searched MEDLINE, Embase, and Web of Science for relevant articles and performed a meta-analysis to investigate the relationship between TLR7 rs179008, rs3853839, rs1790010, TLR4 rs4986791, and rs798690 polymorphisms and SLE. ResultsEighteen studies and 16 papers including 8022 patients with SLE and 9822 healthy controls were retrieved. Meta-analysis revealed that the TLR7 rs179008 T variant was not associated with SLE (OR = 1.008, 95% CI = 0.849–1.394, P = 0.504). Ethnic classification revealed no association between the TLR7 rs179008 T gene and SLE in either European or Latin American groups. Additionally, homozygous comparison, recessive, and dominant models revealed no association between the TLR7 rs179008 variant and SLE. In contrast, a significant association between SLE and the TLR7 rsrs3853839 GG + GA allele (OR = 2.135, 95% CI = 1.502–3.035, <0.001; OR = 23.20, 95% CI = 14.13–38.08, <0.001) was observed in the Arab and Asian groups. The T variant of TLR7 rsrs179010 was also associated with SLE in Asians (OR = 1.177, 95% CI = 1.048–1.321, P = 0.006). In contrast, the TLR4 rs4986791 variant was not associated with SLE in Europeans when allele, homozygous comparison, recessive, and dominant models were used. Furthermore, no association between the TLR4 rs4986790 variant and SLE risk in Europeans was found using any genomic model. ConclusionsMeta-analysis revealed that the TLR7 rs3853839 variant is associated with SLE risk in Asians and Arabs and that TLR7 rs179010 is associated with SLE in Asians. However, TLR7 rs179008, TLR4 rs4986791, and TLR rs798690 polymorphisms were not associated with SLE risk.

The Arg753Gln Polymorphisms in Toll-like Receptor 2 in a Syphilis-Infected and Control Population in The Netherlands: Can Differences in the Number of Self-Reported Sexual Contacts Indicate Protection against Syphilis?

The Arg753Gln polymorphism in Toll-like receptor 2 has been associated with an increased risk of bacterial infections as well as with protection from the late stages of Lyme disease and the acquisition of syphilis. In this study, we determined the presence of this polymorphism in samples collected from men having sex with men/men with women in the Amsterdam Cohort Studies. The presence of the polymorphism was determined by nested PCR, followed by Sanger sequencing. A set of 90 syphilis-seronegative individuals was compared to 95 syphilis-diagnosed participants. A polymorphism allele frequency of 3.9% was found in the control group and 2.63% in the syphilis case group, respectively. None of the individuals showed a homozygous Arg753Gln polymorphism. The number of self-reported sexual contacts was higher in the group of syphilis patients compared to the control group (p = 0.0063). Moreover, in the syphilis case group (n = 49), participants heterozygous for the TLR2-Arg753Gln reported higher numbers of sexual contacts (p = 0.037) compared to wild-type homozygotes. Our findings suggest a possible protective effect of TLR2-Arg753Gln in the acquisition of syphilis. In addition, the determination of the number of self-reported sexual contacts can be used in an evaluation of the protective effect of polymorphism in a population with a low prevalence of it.

Recent advances in different interactions between toll-like receptors and hepatitis B infection: a review.

Hepatitis B virus (HBV) B infections remain a primary global health concern. The immunopathology of the infection, specifically the interactions between HBV and the host immune system, remains somewhat unknown. It has been discovered that innate immune reactions are vital in eliminating HBV. Toll-like receptors (TLRs) are an essential category of proteins that detect pathogen-associated molecular patterns (PAMPs). They begin pathways of intracellular signals to stimulate pro-inflammatory and anti-inflammatory cytokines, thus forming adaptive immune reactions. HBV TLRs include TLR2, TLR3, TLR4, TLR7 and TLR9. Each TLR has its particular molecule to recognize; various TLRs impact HBV and play distinct roles in the pathogenesis of the disease. TLR gene polymorphisms may have an advantageous or disadvantageous efficacy on HBV infection, and some single nucleotide polymorphisms (SNPs) can influence the progression or prognosis of infection. Additionally, it has been discovered that similar SNPs in TLR genes might have varied effects on distinct populations due to stress, diet, and external physical variables. In addition, activation of TLR-interceded signaling pathways could suppress HBV replication and increase HBV-particular T-cell and B-cell reactions. By identifying these associated polymorphisms, we can efficiently advance the immune efficacy of vaccines. Additionally, this will enhance our capability to forecast the danger of HBV infection or the threat of dependent liver disease development via several TLR SNPs, thus playing a role in the inhibition, monitoring, and even treatment guidance for HBV infection. This review will show TLR polymorphisms, their influence on TLR signaling, and their associations with HBV diseases.

Single-nucleotide polymorphisms of TLR4 and GAS7 linked to primary open-angle glaucoma among patients of Shenyang, China.

The potential for adverse outcomes and classifications of glaucoma differ among race, country, gender, and family medical history. Nearly, 50 represent candidate genes are considered as potential contributors to the happening for the primary open-angle glaucoma (POAG) since the advent of GWASs. Our investigation is the first to report the Toll-like receptor 4 (TLR4) and growth arrest-specific 7 (GAS7) among people in Shenyang, China; to investigate whether single-nucleotide polymorphisms (SNPs) in (TLR4) or GAS7 gene are risk factors for POAG among people in Shenyang, China; and also to explore their potential pathogenic mechanisms. POAG patients from July 2015 to June 2019 at Shenyang Fourth People's Hospital were selected. A total of 218 POAG patients and 252 controls were enrolled. Eight potentially functional SNPs of TLR4 (rs7868859, rs7873784, rs77358523, and rs752998) and GAS7 (rs8012311, rs11656696, rs74629981, and rs9900085) were genotyped. Multifactor analysis was conducted to evaluate the correlation between TLR4, GAS7, and POAG. The allele frequency of rs7873784 of TLR4 demonstrated that the GC (P = 0.030), CC (P = 0.040), and GC + CC genotypes (P = 0.009) were significantly higher compared with CC genotype for POAG patients than that for controls. The rs8072311 and rs9900085 of GAS7 gene also were significantly associated with POAG. Haplotype analysis found that the C-A-T-A haplotype (order: rs7873784-rs77358523-rs752998-rs7868859) of TLR4 gene and the two haplotypes A-C-C-A and C-C-A-C of GAS7 (order: rs9900085-rs74629981-rs8072311-rs11656696) were associated with an elevated susceptibility to POAG (P < 0.05). In this study, rs7868859 of TLR4 and rs8012311 and rs9900085 polymorphisms of GAS7 were first identified to be related to POAG among people in Shenyang, China.

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

Background: An increasing number of studies have suggested the relationship between single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes and gastric cancer (GC) susceptibility; however, the available evidence is contradictory. This meta-analysis aimed to comprehensively evaluate whether the SNPs within the TLR family are related to GC development.Methods: PubMed, Scopus, and China National Knowledge Infrastructure (CNKI) were systematically searched up to May 2023 to obtain the pertinent publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were applied to examine the associations using the random-effects model.Results: A total of 45 studies with 25,831 participants (cases: 11,308; controls: 14,523) examining the relation of 18 different SNPs in the TLR family to GC were analyzed. Variations in TLR-4 rs4986790, TLR-4 rs4986791, TLR-5 rs5744174, and TLR-9 rs187084 were significantly associated with increased risk of GC in different genetic models. No significant association was detected for TLR-2-196 to -174de (Delta22), TLR-2 rs3804100, TLR-4 rs11536889, TLR-4 rs11536878, TLR-4 rs2770150, TLR-4 rs10116253, TLR-4 rs1927911, TLR-4 rs10983755, TLR-4 rs10759932, TLR-4 rs1927914, and TLR-10 rs10004195.Conclusion: These findings indicate that variations in TLR-4, TLR-5, and TLR-9 genes were found to be potential risk factors for GC.

Gut Microbiota, Inflammatory Bowel Disease, and Cancer: The Role of Guardians of Innate Immunity.

Inflammatory bowel diseases (IBDs) are characterized by a persistent low-grade inflammation that leads to an increased risk of colorectal cancer (CRC) development. Several factors are implicated in this pathogenetic pathway, such as innate and adaptive immunity, gut microbiota, environment, and xenobiotics. At the gut mucosa level, a complex interplay between the immune system and gut microbiota occurs; a disequilibrium between these two factors leads to an alteration in the gut permeability, called 'leaky gut'. Subsequently, an activation of several inflammatory pathways and an alteration of gut microbiota composition with a proliferation of pro-inflammatory bacteria, known as 'pathobionts', take place, leading to a further increase in inflammation. This narrative review provides an overview on the principal Pattern Recognition Receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), focusing on their recognition mechanisms, signaling pathways, and contributions to immune responses. We also report the genetic polymorphisms of TLRs and dysregulation of NLR signaling pathways that can influence immune regulation and contribute to the development and progression of inflammatory disease and cancer.

Toll-like receptor 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer: a meta-analysis of genetic association studies

BackgroundGastric cancer has a complex aetiology including genetic factors. Individual case-control studies of toll like receptor (TLR) 9 (-1237 T/C, -1486 T/C) polymorphisms in the gastric cancer risk were available, and they showed variation in the findings. Therefore, we performed a meta-analysis to synthesize the evidence on the association between polymorphisms of TLR 9 (-1237 T/C, -1486 T/C) and the risk of gastric cancer using data from eligible studies.MethodsThis study followed the PRISMA 2020 Checklist. Studies were searched in health-related databases. The methodological quality of studies was evaluated with the use of Newcastle-Ottawa Scale criteria. The summary odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and the risk of gastric cancer using five genetic models. Stratification was done by ethnic groups. For the robustness of the analysis, a leave-one-out meta-analysis was performed.ResultsEight case-control studies with 3,644 participants (1914 cases, 1730 controls) were conducted across six countries. Half of the studies were conducted in China. In the NOS methodological quality assessment, only three studies received a high-quality rating (i.e., a score of ≥ 7). TLR 9 (-1486 T/C) polymorphism and the risk of gastric cancer were assessed in six studies, four of Asian ethnicity and two of non-Asian. Under the dominant model, only in the Asian ethnic group showed a marginally and significantly increased risk of gastric cancer (overall: OR = 1.22, 95%CI = 0.90–1.67, I2 = 56%; Asian: OR = 1.24, 95%CI = 1.00-1.54, I2 = 0%, non-Asian: OR = 1.25, 95%CI = 0.38–4.09, I2 = 89%). Under the recessive model in the absence of heterogeneity, only the Asian group had a significantly higher risk of developing gastric cancer (overall: OR = 1.4, 95% CI = 0.74–2.64, I2 = 85%; Asian: OR: 1.41, 95% CI = 1.07–1.86, I2 = 0%, non-Asian: OR = 1.18, 95% CI = 0.12–11.76, I2 = 97%). Under the heterozygous model, there was no significant association with the risk of gastric cancer overall or among any ethnic subgroup. Under the homozygous model in the absence of heterogeneity, only the Asian group had a significantly higher risk of gastric cancer (overall, OR = 1.47, 95% CI = 0.76–2.86, I2 = 82%; Asian: OR = 1.54, 95% CI = 1.13–2.1, I2 = 0%; non-Asian: OR = 1.19, 95% CI = 0.1-14.33, I2 = 96%). Under the allele model, a significantly increased risk of gastric cancer was observed only in the Asian group (overall: OR = 1.23, 95% CI = 0.89–1.71, I2 = 84%; Asian: OR = 1.22, 95% CI = 1.05–1.41, I2 = 0%; non-Asian: OR = 1.24, 95% CI = 0.34–4.59, I2 = 97%). Four studies investigated the association between TLR 9 (-1237 T/C) polymorphism and the risk of developing gastric cancer. Under any of the five genetic models, there was no association between TLR 9 (-1237 T/C) and the development of gastric cancer in overall or in any ethnic subgroup. Sensitivity analysis revealed that the effect was unstable. With a small number of studies with a small number of participants, we addressed the issue of insufficient power for drawing conclusions.ConclusionsThe findings suggested that TLR9 (-1486 T/C) may play a role in the risk of gastric cancer specific to the Asian ethnic group. To substantiate the findings on the association between these two polymorphisms (TLR9 -1237 T/C, -1486 T/C) and the risk of gastric cancer, future well-designed case-control studies with a sufficient number of participants in multi-ethnic groups are recommended.

Role of toll-like receptor in the pathogenesis of oral cancer.

Toll-like receptors are important molecules of innate immunity. They are known as pattern recognition receptors. They recognise certain molecules known as pathogen-associated molecular pattern on a pathogen and release chemicals that causes inflammation. Toll-like receptors (TLR) help in the removal of the infected cell and thus stop the spread of infection and are being studied for their association with cancer. Oral carcinoma has emerged as a major problem of our country today; it is found ranks first in men and third in women. Toll-like receptors have been implicated in the development of cancer. Certain polymorphisms in toll-like receptor can make a cell more susceptible to develop oral cancer. The identification of toll-like receptors and the different genotypes that are involved in the development of cancer can be utilised for using them as biomarkers of the disease. The study revealed that toll-like receptors like TLR7 and TLR5 are found to have a role in suppression of oral cancer while toll-like receptors like TLR4 and TLR2 are found to be associated with the progression of oral cancer. Toll-like receptors can turn out as important target molecules in the future in designing therapeutic strategies for oral cancer.

Polymorphism of Toll-like Receptor 4 is Correlated with an Increased Risk of Mortality of Hemodialysis Patients: A Retrospective Cohort Study in Taiwanese

Polymorphism of Toll-like Receptor 4 is Correlated with an Increased Risk of Mortality of Hemodialysis Patients: A Retrospective Cohort Study in Taiwanese

The Emerging Role of Toll-Like Receptor-Mediated Neuroinflammatory Signals in Psychiatric Disorders and Acquired Epilepsy.

The new and evolving paradigms of psychiatric disorders pathogenesis are deeply inclined toward chronic inflammation that leads to disturbances in the neuronal networks of patients. A strong association has been established between the inflammation and neurobiology of depression which is mediated by different toll-like receptors (TLRs). TLRs and associated signalling pathways are identified as key immune regulators to stress and infections in neurobiology. They are a special class of transmembrane proteins, which are one of the broadly studied members of the Pattern Recognition Patterns family. This review focuses on summarizing the important findings on the role of TLRs associated with psychotic disorders and acquired epilepsy. This review also shows the promising potential of TLRs in immune response mediated through antidepressant therapies and TLRs polymorphism associated with various psychotic disorders. Moreover, this also sheds light on future directions to further target TLRs as a therapeutic approach for psychiatric disorders.

Salivary IL-33 and sST2 levels in relation to TLR2 rs111200466 polymorphism and periodontitis.

Toll-like receptor-2 (TLR2) signalling pathway is involved in the regulation of interleukin (IL)-33 and its receptor suppression of tumorigenicity-2 (ST2). This study aimed to compare salivary IL-33 and soluble ST2 (sST2) levels of periodontitis patients with those of periodontally healthy individuals in relation to their TLR2 rs111200466 23-bp insertion/deletion polymorphism within the promoter region. Unstimulated saliva samples were collected, and periodontal parameters were recorded from 35 periodontally healthy individuals and 44 periodontitis patients. Non-surgical treatments were applied to periodontitis patients, and sample collections and clinical measurements were repeated 3 months following therapy. Salivary IL-33 and sST2 levels were measured with enzyme-linked immunosorbent assay kits, and TLR2 rs111200466 polymorphism was detected by polymerase chain reaction. Elevated salivary IL-33 (p = 0.007) and sST2 (p = 0.020) levels were observed in periodontitis patients, in comparison to controls. sST2 levels declined 3-months following treatment (p < 0.001). Increased salivary IL-33 and sST2 levels were found to be associated with periodontitis, with no significant relation to the TLR2 polymorphism. Periodontitis, but not TLR2 rs111200466 polymorphism, is associated with elevated salivary sST2 and possibly IL-33 levels, and periodontal treatment is effective in reducing salivary sST2 levels.

Systemic lupus erythematosus and toll-like receptor 9 polymorphisms: A meta-analysis of genetic association studies.

This study aimed to examine whether polymorphisms in toll-like receptor 9 (TLR9) contribute to vulnerability to systemic lupus erythematosus (SLE). We searched the MEDLINE, Embase, and Web of Science databases for relevant articles. We conducted a meta-analysis to examine the association between the TLR9 rs187084, rs352139, rs352140, and rs5743836 polymorphisms and SLE risk. A total of 5447 patients with SLE and 6588 control participants across 26 trials from 24 articles were included. The TLR9 rs187084 T allele was significantly associated with SLE (odds ratio, 1.146; 95% confidence interval, 1.033-1.273; p = 0.010). In a meta-analysis, the TLR9 rs187084 T allele was associated with SLE in the Asian population but not in the Arab population, demonstrating the existence of ethnicity-specific effects. Using homozygote contrast and recessive models, the researchers also found that the TLR9 rs187084 T/C polymorphism was associated with SLE. The TLR9 rs352139 G allele was not associated with SLE in this meta-analysis. After accounting for ethnic differences, we found that the TLR9 rs352139 G allele was not associated with SLE in Asians and Arabs. Furthermore, homozygote contrast and dominant models found no association between the TLR9 rs352139 G/A polymorphism and SLE. TLR9 polymorphisms at rs352140 and rs5743836 were not associated with an increased risk of SLE in any genetic prediction model, including people of Asian, European, or Latin American ancestry. SLE susceptibility is associated with the TLR9 rs187084 polymorphism in the Asian population and the rs187084, rs352139, rs352140, and rs5743836 polymorphisms in the Asian, European, and Latin American populations, respectively.

Genetic Polymorphism of TLR5 and TLP6 in Iraqi Patients with Heart Failure Disease

In spite of the high rate of morbidity and mortality heart failure (HF) is common, and none of the medications are now entirely available for HF treatment. In addition to many environmental influences and clinical diseases, genetic factors may also contribute to the progression and development of HF. In the current study, samples of blood were collected from 150 heart failure patients and 130 healthy controls. We evaluated the association of four single nucleotide polymorphisms (snps) of Toll-like receptors (TLR6 and TLR5) with (HF) susceptibility in the Iraqi population. In this work, (SNP) called Toll-like receptor 5 (rs5744168, rs2072493) and Toll-like receptor 6 (rs1039559, rs5743810) were employed. (PCR-RFLP) for snps (rs5744168, rs2072493, and re5743810), and sequencing for snps were used to assess the allele and genotype frequencies in both the patient and control groups (rs1039559). In patients with heart failure and healthy controls, a significant difference was discovered in the genotypic and allelic frequencies of snps. From our results, we suggest that these snps act as a potential predisposing factor for HF development.