Toll-like Receptor 4 Polymorphisms Research Articles

The Arg753Gln Polymorphism of Toll-Like Receptor 2 Has a Lower Occurrence in Patients with Syphilis, Suggesting Its Protective Effect in Czech and Slovak Individuals.

Syphilis is a bacterial infection caused by Treponema pallidum subsp. pallidum Infection with T. pallidum subsp. pallidum and its dissemination lead to the synthesis of proinflammatory cytokines triggered by the interaction of bacterial lipoproteins with Toll-like receptor 2 (TLR2). TLR2 contains several nonsynonymous single-nucleotide polymorphisms that may impact the activation of its signaling cascade and alter the responsiveness to, or the course of, various infectious diseases, including those caused by pathogenic spirochetes. To investigate whether TLR2 polymorphism may influence susceptibility to syphilis, 221 healthy individuals with no history of syphilis (controls) and 137 patients diagnosed with syphilis (cases) were screened for the presence of the Arg753Gln polymorphism in the TLR2 gene (2258G→A; rs5743708). The Arg753Gln variant occurs at a significantly lower frequency in syphilis patients (4 of 137 [3%]) than in controls (24 of 221 [10.9%]). These data suggest that TLR2 Arg753Gln may protect from the development of syphilis due to reduced signaling.

Genetic variants in the regulation region of TLR4 reduce the gastric cancer susceptibility.

Gastric cancer (GC) is one of the most common cancers diagnosed in China. It has been suggested that the genetic polymorphisms of Toll-like receptors (TLRs) might be in close relation to tumorigenesis and development of gastric cancer. In this study, we performed a case-control study to investigate the genetic polymorphisms of TLR3, 4, 5, 7 with the genetic susceptibility of gastric cancer. TLRs gene polymorphisms in 471 gastric cancer (GC) patients and 471 healthy controls were analyzed by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis or TaqMan assays. Odds ratio (OR) and its 95% confidence interval (95%CI) were used to evaluate the association of TLR4 variants with the GC risk via unconditional logistic regression. Our results suggested that variant genotypes of TLR4 rs7869402 (OR=0.61, 95%CI=0.40-0.92, P=0.02) and TLR4 rs7873784 (OR=0.17, 95%CI=0.09-0.33, P<0.01) gene polymorphisms reduced the risk of GC. Stratified analysis showed that rs7869402 T-containing genotype significantly decreased the susceptibility of GC among females (OR=0.38, 95%CI=0.16-0.91, P=0.03), older subjects (OR=0.48, 95%CI=0.26-0.87, P=0.02), non-smokers (OR=0.41, 95%CI=0.23-0.71, P<0.01) and non-drinkers (OR=0.58, 95%CI=0.30-0.78, P<0.01). In case of rs7873784 polymorphism, C-containing genotype reduced the risk of GC among males (OR=0.08, 95%CI=0.03-0.21, P<0.01), but not among females (OR=0.53, 95%CI=0.22-1.27, P=0.15). As to the other four SNPs (TLR3 rs5743303, TLR4 rs1927914, TLR5 rs1640816 and TLR7 rs3853839), no significant correlations were found to be related to the risk of gastric carcinoma. Our research demonstrated the significance of TLRs polymorphisms in decreasing the risk of GC.

Interactive effect of TLR SNPs and exposure to sexually transmitted infections on prostate cancer risk in Jamaican men.

Prostate cancer (PC) risk increases with African ancestry and a history of sexually transmitted infections (STIs). Also, single-nucleotide polymorphisms (SNPs) in toll-like receptor (TLR) genes influence PC risk. This pilot study explores interactions between STIs and TLR-related SNPs in relation to PC risk among Jamaican men. This case-control study evaluates two TLR related SNPs in 356 Jamaican men (194 controls and 162 cases) with or without history of STIs using stepwise penalized logistic regression in multivariable analyses. Age (odds ratio [OR] = 1.08; 95% confidence interval [CI]: 1.04-1>.12; p < .001) and IRF3_rs2304206 GG genotype (OR = 0.47; 95% CI: 0.29-0<.78; p = .003) modulated PC risk in people with history of STIs. In the population with no history of STIs, resulting interactions between risk factors did not survive correction for multiple hypothesis testing. Overall, an interaction between the IFR3_rs2304206 variant and a history of exposure to STIs leads to greater decrease of PC risk than the presence of polymorphic genotype alone. These findings are suggestive and require further validation. Identification of gene variants along with detection of lifestyle behaviors may contribute to identification of men at a greater risk of PC development in the population.

Insights into the toll-like receptors in sexually transmitted infections.

Toll-like receptors (TLRs) are like soldiers of an innate immune system, which protects vital biological processes against invading pathogens. TLR signalling pathways help in the removal of pathogens and mediate well-established inflammatory processes. However, these processes may also aid in the development or augmentation of an infection or an autoimmune disease. Recent studies have delineated TLR polymorphism's role in the loss of function, making hosts more resistant or vulnerable to the development of an infection. In this review, we have discussed the association of TLRs with sexually transmitted infections (STIs), especially to the pathogen-specific ligands. We have also assessed the impact on TLR downstream signalling and the maintenance of cellular homeostasis during immune responses. Besides, we have discussed the role of TLRs single nucleotide polymorphisms in various STIs. Since TLRs are known to play a part in defence mechanisms and in aiding infections therefore, a thorough understanding of TLRs structure and molecular mechanisms is required to explain how they can influence the outcome of an STI. Such a strategy may lead to the development of novel and useful immunotherapeutic approaches to control pathogen progression and prevent transmission.

Role of Toll-Like Receptors 2 and 4 Genes Polymorphisms in Neonatal Sepsis in a Developing Country: A Pilot Study

Abstract Objective Toll-like receptors (TLR) are one of the key molecules that alert the immune system to the presence of microbial infections. This study attempts to elucidate the role of TLR2 and TLR4 polymorphisms in neonatal sepsis. Methods A case–control study including 30 neonates with confirmed sepsis compared with 20 neonates in a control group. TLR2 and TLR24 gene polymorphisms were confirmed by polymerase chain reaction. Results The majority of infections were attributed to gram-negative organisms (72.5%) namely Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Results also revealed that incidence of TLR polymorphism was significantly different between the sepsis and control groups (p = 0.016). The most common polymorphism was TLR2; Arg 753 Gln (16.7%). Presence of TLR polymorphism was also associated with a longer duration of therapy (a median of 10 days for cases with positive polymorphism compared with 6.5 days for negative cases; p = 0.001). Conclusion This pilot study suggests that any polymorphisms in TLR2 and TLR4 might have a role that interferes with the innate immune response of newborn.

The analysis of the top 100 most cited publications in chest diseases in Turkey (1975-2019): a bibliometric analysis.

In this study, made an analysis of the top 100 most-cited articles about respiratory system from Turkey, which was published in Science Citation Index (SCI) and SCI Expanded (SCIE) index. In Web of Science (WoS) advanced search of the database of "core collection" [v.5.31]; It was written to "CU=TURKEY AND SU=RESPIRATORY SYSTEM" and reached articles from Turkey published in SCI and SCIE indexes until 13.11.2019. The journal in which it was published, the impact factor of the journals, citation counts and the average of the annual citations of the publication of the first 100 articles were found. From 1975 to 13 November 2019, the total number of publications in the field of respiratory system by the scientists of our country was 5828. The total number of citations to these articles is 48.708 (with subtracting the self citations it was 46.972). The average of citations per publication in our country is 8.36. The total number of citations for the first 100 articles was 12.374. The most cited article with 309 citations is; "The Arg753Gln Polymorphism of the Human Toll-like Receptor 2 Gene in Tuberculosis Disease" written by Ogus AC, et al. It was published in "European Respiratory Journal". Until 13.11.2019 in WoS database related to respiratory system; It has been published 494.974 articles. Published articles from Turkey is 1.17% of the total articles about respiratory system. Although there are our studies have been published in journals with high impact factors, our contribution to the literature still seems limited.

TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects.

Background: Activation of Toll-like-receptor 4 (TLR4) causes chronic inflammation that can result in obesity and metabolic syndrome (MeS). Aim: This study aimed to investigate the role of TLR4 polymorphisms of TLR4D299G/T399I, and its impact on protein expression of TLR4 in obese female subjects. Methodology: A prospective cross-sectional association study was performed on Arab female subjects from Qatar University. The subjects were categorized according to BMI classifications into two groups: “obese; n = 69” and “non-obese; n = 136”. Anthropometric measurements, weight (kg), height (m) and waist circumference (WC) were evaluated, and the body mass index (BMI) was calculated. Fasting blood samples were collected, and assessment of glucose, lipid profile, C-reactive protein (CRP), leptin, IL-6 and insulin was performed. Insulin resistance was computed using HOMA-IR. Genotyping of the TLR4 polymorphisms of TLR4D299G (rs4986790) and TLR4T399I (rs4986791) was performed by the 5′ nuclease assay by TaqMan MGB probe. Flow cytometry was used to evaluate the monocyte cell surface expression of TLR4. Results: The frequency distribution of the genotype revealed that homozygous AA is the most frequent among obese subjects (86.4%) for (TLR4D299G, A > G) and the homozygous CC genotype is the most frequent (92.4%) for (TLR4T399I, C > T). Haplotype analysis of TLR4 D299G/T399I showed that GT carriers had a significant association with increased probability of insulin resistance (odds ratio = 4.73; 95% CI 1.19–18.90; p-value = 0.016). The monocyte cell surface of TLR4 was significantly higher by 1.3 folds in obese compared to non-obese subjects. Conclusions: TLR4 D299G/T399I haplotype polymorphism is associated with an increased risk of insulin resistance with the upregulation of TLR4 protein expression in obese subjects.

Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease.

IntroductionInflammation plays a major role in the development of atherosclerosis and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. Toll-like receptor-4 (TLR4) is a major receptor for lipopolysaccharides (endotoxin) and other ligands involved in the pathogenesis of inflammation. We determined whether endotoxin levels and the presence of TLR4 polymorphisms are associated with markers of inflammation and atherosclerosis among South African CKD patients.Materials and methodsEndotoxin, lipopolysaccharide binding protein (LBP), serum CD14 (sCD14), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and carotid intima media thickness (CIMT) were measured in 160 participants (120 CKD patients and 40 controls). Associations between endotoxins and CIMT in the presence of sCD14, IL-8 and MCP-1, were assessed using odds ratios. Participants were screened for the presence of Asp299Gly and Thr399Ile TLR4 polymorphisms, and CIMT and inflammatory markers were compared between subjects with and without TLR4 polymorphisms.ResultsEndotoxin levels correlated with sCD14 (r = 0.441, p<0.001) and MCP-1 (r = 0.388, p<0.001) levels while increased CIMT was associated with MCP-1 (r = 0.448, p<0.001), sCD14 levels (r = 0.476, p<0.001), LBP (r = 0.340, p<0.001), and IL-8 (r = 0.395, p<0.001). Atherosclerosis was associated with endotoxin levels (odds ratio: 4.95; 95% confidence interval: 2.52–9.73; p<0.001), and was predicted by higher serum levels of inflammatory markers. Analysis of patients with TLR4 polymorphisms showed reduced serum levels of inflammatory markers and CIMT values compared with the patients carrying the wild type TLR4 alleles.ConclusionThe study demonstrated associations between circulating endotoxaemia, systemic inflammation and accelerated atherosclerosis among South African CKD patients, and showed that the atherogenic predictive power of endotoxaemia was significantly increased by the presence of elevated levels of inflammatory markers. Additional findings, which must be confirmed, suggest that TLR4 polymorphisms are associated with low levels of inflammatory markers and CIMT values.

Interrelationship between Toll-like receptors and infection after orthotopic liver transplantation.

Early microbial recognition by the innate immune system is accomplished by Toll-like receptors (TLRs), with resultant initiation of a pro-inflammatory response against infecting organisms. In spite of presence of an abundance of Toll-like receptors on the surface of the liver, gut bacteria does not elicit an inflammatory reaction in healthy individuals due to tolerance to these TLRs, suggesting that the inflammatory responses seen in the liver are the result of breakdown of this tolerance. While orthotopic liver transplantation is often life saving in many instances, death following this procedure is most commonly due to infection that occurs in up to 80% of transplant recipients, most commonly due to microbial causes in up to 70% of cases and viral infections in 20%, while fungal infections affect only 8% of cases. The probability of acquiring infection following hepatic transplantation is heightened due to affection of the innate immune defense mechanisms of the host following this procedure. Single nucleotide polymorphisms of TLRs have been associated with increased likelihood of either development of post-transplant infection or eradication of infecting organism. However, conflicting reports from other studies reveal that prevalence of this single nucleotide polymorphism is not increased in infected patients.

Polymorphisms in Toll-like receptors 1, 2, 5, and 10 are associated with predisposition to Helicobacter pylori infection.

Toll-like receptors (TLRs) are significant receptors to the innate immune system which symbolizes a family of pattern recognition receptors. We aimed to investigate associations between rs4833095 polymorphism of TLR1, rs3804099 polymorphism of TLR2, rs5744174 polymorphism of TLR5, and rs10004195 polymorphism of TLR10 in dyspeptic individuals with Helicobacter pylori infection. Genomic DNA was isolated and genotyping of rs4833095 polymorphism in TLR1, rs3804099 polymorphism in TLR2, rs5744174 polymorphism in TLR5, and rs10004195 polymorphism in TLR10 were investigated in 400 individuals (205 in dyspeptic individuals with H. pylori-positive subjects and 195 dyspeptic individuals with H. pylori-negative subjects) by real-time PCR. Statistical analysis was performed by Pearson's Chi-square test. According to our study; rs4833095 polymorphism in TLR1 C allele, rs3804099 polymorphism in TLR2 C allele, rs5744174 polymorphism in TLR5 C allele, and rs10004195 polymorphism in TLR10 A allele increased the risk of H. pylori infection [odds ratio (OR), 2.01; 95% confidence interval (CI), 1.39-3.16; OR, 1.78; 95% CI, 1.19-2.6; OR, 1.87; 95% CI, 1.25-2.78; OR, 2.66; 95% CI, 1.72-4.099, respectively]. This is the first study that investigates TLRs in H. pylori infection in Turkey. Our findings may support the hypothesis that polymorphisms in certain TLRs may cause a genetic predisposition to H. pylori-related gastric problems.

Diversity of Toll-like Receptor Genes and Helicobacter Pylori Infections: A Meta-Analysis Study

Background and Aims: Several studies have shown that host genetic factors can be associated with the risk of developing Helicobacter pylori infections. Therefore, we evaluated the most prevalent toll-like receptors (TLRs) polymorphisms in Helicobacter pylori positive subjects and their possible role in susceptibility to Helicobacter pylori infections. Materials and Methods: Using related keywords, an independent search in the electronic databases including PubMed, Scopus, Google Scholar and ISI web of knowledge was performed to collect studies evaluating, until January 15, 2019, polymorphisms in the TLR 1 to 13 genes and their association with susceptibility to Helicobacter pylori infection. A total of 18 articles met our inclusion criteria and thus were included in the meta-analysis. Results: In this meta-analysis, a significantly increased risk of Helicobacter pylori infection was observed in subjects carrying TLR2 rs3804099 (TT vs. CC: odds ratio = 2.209, 95% CI: 1.283-3.804), TLR4 rs4986790 (A allele vs. G allele: odds ratio = 2.987, 95% CI: 1.899-4.697), TLR4 rs4986791 (C allele vs. T allele: odds ratio = 5.469, 95% CI: 13.432-8.713), TLR4 rs4986791 (CC vs. TT: odds ratio = 7.974, 95% CI: 2.682-23.706), TLR4 rs10759932 (TT vs. CC: odds ratio = 3.180, 95% CI: 1.022-9.890), TLR4 rs1927914 (C allele vs. T allele: odds ratio = 8.831, 95% CI: 4.222-18.470), and TLR9 rs352140 (CC vs. CT: odds ratio = 1.878, 95% CI: 1.071-3.290) polymorphisms. Conclusions: This meta-analysis indicated that TLR2 rs3804099, TLR4 rs4986790, TLR4 rs4986791, TLR4 rs10759932, TLR4 rs1927914 and TLR9 rs352140 polymorphisms are associated with increased susceptibility to Helicobacter pylori infections.

Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy

BackgroundMaternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans.MethodsIn a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R.ResultsThe TLR7 rs179008A > T (p < 0.001) polymorphism was associated while the TLR9 rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6 rs10499563T > C (p < 0.001) and TLR2 rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7, IL-6, IL-10, IL-28B, IL-1A and interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations.ConclusionsToll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.

TLR4 Polymorphisms (896A>G and 1196C>T) Affect the Predisposition to Diabetic Nephropathy in Type 2 Diabetes Mellitus.

PurposeType 2 diabetes mellitus (T2DM) is a disease with a steadily increasing incidence throughout the world. Some molecules regulating the innate immune responses such as toll-like receptor 4 (TLR4) have shown to be involved in late diabetic complications. This study aimed to investigate the association of TLR4 gene polymorphisms with clinicopathological aspects of T2DM in the Iranian population.Patients and MethodsTwo TLR4 896A>G and 1196C>T polymorphisms were assessed in 100 T2DM patients and 100 healthy controls using sequence-specific primers PCR. Demographic, anthropometric, and biochemical parameters were obtained from the participants.ResultsAfter logistic regression, in 1196C>T, a significant association was shown between diabetic nephropathy (DN) and CT genotype (P= 0.04, OR= 4.35, CI= (1.04–18.1)). TG level has increased significantly in both T2DM and control subjects with CT genotype (P= 0.027, OR= 1.005, 95% CI= (1.001–1.01)). For 896A>G variant, a significant association was also detected between AG genotype and increased oral glucose tolerance test (OGTT) level (P= 0.048, OR= 1.003, 95% CI= (1.00–1.005)).ConclusionAlthough minor alleles of 1196C>T and 896A>G variants have not directly been associated with type 2 diabetes, by involving in the dysregulation of serum TG and blood sugar levels, they might increase the risk of DN.

Study of Toll‑Like Receptor 4 Gene Polymorphisms in Colorectal Cancer: Correlation with Clinicopathological Features

ABSTRACT Polymorphisms of Toll-like receptor 4 (TLR4) as a key player in cell proliferation, apoptosis, and angiogenesis have been linked to colorectal cancer (CRC) in different populations. We aimed in this study to determine genetic associations of TLR4 variants with CRC progression in Egyptian patients. Genotype and allelic frequencies of Asp299Gly (rs4986790) and Thr399Ile (rs4986791) were compared between 127 CRC patients and 141 healthy Egyptians using restriction fragment length polymorphism, and were correlated to clinicopathological findings. Results revealed that the variant alleles (G of Asp299Gly) and (T of Thr399Ile) were significantly associated with CRC among Egyptians. Confirmed by haplotype analysis, AT and GT haplotypes were more frequent in CRC patients than controls with increased CRC odds (OR = 3.54 and 3.45, 95% CI = 1.48–8.48 and 1.09−10.83, respectively). In addition, the G allele of Asp299Gly SNP was observed to be significantly associated with progressive CRC, including stage IV (P = .001), grade III (P = .025), N2 lymph nodes (P = .020), and metastasis (P = .001). On the other hand, Thr399Ile variant did not show any association with tumor behavior. Taken together, we conclude a significant association of Asp299Gly and Thr399Ile variants with the risk of development of CRC in Egypt. Asp299Gly variant, but not the Thr399Ile variant, may serve as a biomarker of this disease progression in Egyptian population.

THE ASSOCIATION BETWEEN GENETIC POLYMORPHISMS OF TOLL-LIKE RECEPTORS AND MANNOSE-BINDING LECTIN AND ACTIVE TUBERCULOSIS IN HIV-INFECTED PATIENTS

Objectives: to analyze the association between genetic polymorphisms of Toll-like receptors (TLR) and mannose-binding lectin (MBL) and active tuberculosis in HIV-infected patients to consider the possibility of using genetic markers as a way to personalize the chemoprophylaxis of tuberculosis in this category of patients. Materials and methods : The study enrolled 171 patients (85 HIV-infected, 86 HIV/TB co-infected patients). Single nucleotide polymorphisms (SNP) in the TLR4 (rs4986790), TLR2 (rs5743708) and MBL2 (rs5030737, rs1800450, rs1800451) were genotyped by real-time PCR and pyrosequencing. Data about epidemiological risk factors were obtained from epidemiological anamnesis. Immune status was assessed by the level of CD4+ T-cells count. Results : Statistically significant association with active tuberculosis was identified for the genotype AG of TLR4, rs4986790 (OR=5.2; 95% CI: 1,8–14,6, p=0,002). Multivariate analysis shows that close contact with TB patientand status of ex-prisoner increased the risk of active tuberculosis 5,2 times (OR=5,2; 95% CI: 1,4–18,5, p=0,012 and OR=5,2; 95% CI: 1,5–17,7, p=0,009, respectively); CD4+ T-cell count more than 200 cells/mm 3 exerted protective effect and reduced the risk of developing TB 5 times (OR=0,2; 95% CI: 0,1–0,5, p=0,001). The genotype AG of TLR4, rs4986790 increased the risk of active tuberculosis 3,7 times (OR=3,7; 95% CI: 1,1–13,1, p=0,046). Conclusion . The G allele of TLR4, rs4986790 can be considered as an independent risk factor for active tuberculosis in HIV-infected individuals. These results need to be confirmed by further investigations on large samples.

Association of disease severity with toll-like receptor polymorphisms in multidrug-resistant tuberculosis patients.

The disease severity in pulmonary Multidrug-resistant tuberculosis (MDR-TB) varies from mild to severe, which is determined by host and pathogen virulence factors. The difference of symptoms felt by TB patients were interesting to investigate in discovering whether its the human immune response or bacteria's virulence gene that plays the role. The aim of this research was to analyze association between disease severity degree of pulmonary MDR-TB patients with Single nucleotide polymorphisms (SNPs) found in toll-like receptors (TLRs) gene. Blood samples were obtained from pulmonary MDR-TB patients in Dr. Soetomo Hospital, Surabaya, Indonesia. Polymerase chain reaction (PCR) multiplex and target SNPs were analyze using DigiTag2 assay. The variant of esxA gene was determined using PCR and sequencing. Severity degree was determined by chest X-ray, the lesions were scored according to their severity, score of =2.5 ranking as mild, 2.5-6 as moderate and =6 as severe. Association level between SNP in TLRs gene degree of pulmonary MDR-TB was analyzed using Chi-square test. Bonferroni correction for multiple comparison was used to anticipate genotyping error. A total of 22 MDR-TB patients were classified into severe degree group, while 16 patients were moderate/mild degree. SNPs in encoding gene of TLRs were mostly found in intron, specifically in TLR-1, TLR-2, and TLR-6. HWE P value in rs5743572 was 0.841; in rs3804100 was 0.0176; and in rs5743808 was 0.562. Association analysis between SNP in TLRs genes and degree of disease revealed significant association in rs5743572, SNP of TLR-1, with P < 0.05; odds ratio [OR] = 11.67 (95% confidence interval [CI]: 3.94-34.52); rs3804100, SNP of TLR-2 had P < 0.05; OR = 37.59 (95% CI: 9.30-151.88); and rs5743808, the SNP of TLR-6 had P < 0.05; OR = 31.5 (95% CI: 8.60-115.34). We concluded that SNPs in TLR-1, TLR-2, and TLR-6 of pulmonary MDR-TB patients was found to have an association with disease severity. TLRs polymorphism had significant association was present in TLR-1 rs5743572 in intron, TLR-2 rs3804100 in exon, and TLR-6 rs5743808 in exon and among MDR-TB isolates from patients with pulmonary MDR-TB of severe and moderate/mild degree.

-196 to -174del, rs4696480, rs3804099 polymorphisms of Toll-like receptor 2 gene impact the susceptibility of cancers: evidence from 37053 subjects.

Relationship between Toll-like receptor-2 (TLR2) and cancer risk has been illustrated in some studies, but their conclusions are inconsistent. Therefore, we designed this meta-analysis to explore a more accurate conclusion of whether TLR2 affects cancer risks. Articles were retrieved from various literature databases according to the criteria. We used STATA to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the relationship between certain polymorphism of TLR2 and cancer risk. Finally, 47 case–control studies met the criteria, comprising 15851 cases and 21182 controls. In the overall analysis, people are more likely to get cancer because of -196 to -174del in TLR2 in all five genetic models, B vs. A (OR = 1.468, 95% Cl = 1.129–1.91, P=0.005); BB vs. AA (OR = 1.716, 95% Cl = 1.178–2.5, P=0.005); BA vs. AA (OR = 1.408, 95% Cl = 1.092–1.816, P=0.008); BB+BA vs. AA (OR = 1.449, 95% Cl = 1.107–1.897, P=0.007); BB vs. BA+AA (OR = 1.517, 95% Cl = 1.092–2.107, P=0.013). Meanwhile, rs4696480 could significantly increase the risk of cancer in Caucasians, furthermore, rs3804099 significantly decreased cancer risk in overall analysis, but more subjects are necessary to confirm the results. All in all, this meta-analysis revealed that not only -196 to -174del increased the risk of among overall cancers, Caucasians are more likely to get cancer because of rs4696480, while rs3804099 polymorphism could reduce the risk of cancer in some genetic models. There is no direct evidence showing that rs5743708, rs3804100 and rs1898830 are related to cancer.

ПОЛИМОРФИЗМ ГЕНОВ TOLL-ПОДОБНЫХ РЕЦЕПТОРОВ И АССОЦИИРОВАННЫЕ С НИМ ЗАБОЛЕВАНИЯ

ПОЛИМОРФИЗМ ГЕНОВ TOLL-ПОДОБНЫХ РЕЦЕПТОРОВ И АССОЦИИРОВАННЫЕ С НИМ ЗАБОЛЕВАНИЯ

Dectin-1 rs3901533 and rs7309123 Polymorphisms Increase Susceptibility to Pulmonary Invasive Fungal Disease in Patients with Acute Myeloid Leukemia from a Chinese Han Population.

This study aimed to assess whether genetic variants of dendritic cell-associated C-type lectine-1 (Dectin-1), Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) influence the susceptibility to pulmonary invasive fungal disease (IFD) in patients with acute myeloid leukemia (AML) from a Chinese Han population. Eight single nucleotide polymorphisms (SNPs) of Dectin-1 (rs16910526, rs3901533, and rs7309123), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791) and MyD88 (rs4988453 and rs4988457) in the genomic DNA of 172 adult AML patients were genotyped. Pulmonary IFD was diagnosed as proven or probable according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus guidelines. SNPs that were significant in the univariate analysis were further analyzed using the multiple logistic regression analysis to determine their association with the occurrence of pulmonary IFD. The mRNA expression of Dectin-1 was detected according to the genotype by quantitative realtime PCR (qRT-PCR), and the correlation of this expression with the occurrence of pulmonary IFD in AML patients was analyzed. Two Dectin-1 intron SNPs (rs3901533 and rs7309123) were found to be significantly associated with the susceptibility to pulmonary IFD in AML patients in a Chinese Han population. Significant associations were noted between pulmonary IFD and Dectin-1 rs3901533 dominant model (G/T+G/G vs. T/T, OR: 2.158; 95% CI: 1.109-4.2, P=0.02), Dectin-1 rs3901533 G allele (OR: 2.201; 95% CI: 1.206-4.019, P=0.01), or Dectin-1 rs7309123 C allele (OR: 1.919; 95% CI: 1.047-3.518, P=0.03). There were no significant associations between pulmonary IFD and the remaining Dectin-1 SNPs (rs16910526), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791) or MyD88 (rs4988453 and rs4988457). In conclusion, two Dectin-1 SNPs (rs3901533 and rs7309123) are associated with increased susceptibility to pulmonary IFD in AML patients in a Chinese Han population.

TLR4 polymorphisms may increase susceptibility to periodontitis in Pg-positive individuals.

ObjectiveTo investigate the correlation between the single nucleotide polymorphisms (SNPs) in the toll-like receptor 4 (TLR4) gene and the susceptibility to chronic periodontitis.Design241 Chinese subjects from the cohort of Beijing Shijingshan Community were recruited. Buccal swab samples, the whole unstimulated saliva and periodontal clinical parameters were collected. Human DNA extracted from buccal swab samples were used for genotyping eight SNPs of the TLR4 gene (rs11536889, rs1927906, rs1927911, rs2149356, rs4986790, rs4986791, rs2737190, rs787384) by the Sequenom MassARRAY system. Porphyromonas gingivalis (P. gingivalis) was detected from the deposition of the whole unstimulated saliva through polymerase chain reaction (PCR) method based on 16S rRNA. The correlation between SNPs of TLR4 and chronic periodontitis susceptibility in the whole subjects and the patients detected with P. gingivalis was investigated.ResultsThe variants of rs4986790 and rs4986791 were not found in 241 Chinese subjects. Moreover, there was no significant difference in the distribution of theother6 SNPs of TLR4 between groups of none/mild -periodontitis and moderate/severe-periodontitis subjects. When combined with P. gingivalis infection, rs1927911 (TT/CC+CT), rs2149356 (TT/GG+GT) and rs2737190 (GG/AA+AG) were independent risk factors of chronic periodontitis.ConclusionThree SNPs of TLR4, i.e., rs1927911 (TT/CC+CT), rs2149356 (TT/GG+GT) and rs2737190 (GG/AA+AG), were associated with moderate/severe chronic periodontitis in Chinese population infected with P. gingivalis. P. gingivalis, which interacted with TLR4 gene plays an important role in the pathogenesis of periodontitis.