Toll-like Receptor 4 Single Nucleotide Polymorphisms Research Articles

Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer

Exposure to solar ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4)-mediated immune dysregulation has emerged as a key mechanism for the detrimental effects of acute and chronic UV exposure and skin cancer in mice. Single nucleotide polymorphisms (SNPs) on the TLR4 gene have been reported to increase or decrease susceptibility to various cancers in other organs. There is limited information on TLR4 SNPs and susceptibility to human keratinocyte carcinomas. The study’s objective is to test the association between TLR4 SNPs and the risk of developing keratinocyte carcinomas. Skin cancer patients and controls at the University of Alabama at Birmingham completed a cross-sectional survey on personal and family history of skin cancer as well as on sunscreen use and tanning proneness. Peripheral blood samples were obtained from participants, and DNA was extracted to genotype the TLR4 SNPs. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association between TLR4 SNPs and skin cancer risk. The sample consisted of a cohort of 93 skin cancer patients over the age of 50 and 94 controls; 33.3% of cases and 44.7% of controls were females; 12.9% of cases and 17% of controls had a TLR4 SNP. The most common SNP was D299G/T399I in 9.7% of skin cancer patients and 13.8% of controls. We did not find a statistically significant association between the D299G/T399I SNP and skin cancer (odds ratio (OR) = 0.34, 95% CI: 0.11, 1.07, p = 0.065) adjusting for age, sex, eye color, actinic keratosis, sunscreen use and reapplication, and family history of skin cancer. Based on our findings from our limited cohort of participants, we found some protective effect for the TLR4 SNP for skin cancer, which was not statistically significant. Validation of these findings in a larger cohort is warranted.

Toll-like receptor 9 (TLR9) genetic variants rs187084 and rs352140 confer protection from Behcet’s disease among Iranians

BackgroundBehcet’s disease (BD) is a multisystem and multifactorial autoimmune disease characterized by relapsing episodes of oral aphthae, genital ulcers, and ocular and skin lesions. Toll-like receptor 9 (TLR9) has pro-inflammatory roles and its genetic variants might be involved in the pathogenesis of inflammatory diseases. MethodsTwo hundred five BD patients and 207 age and sex-matched healthy controls were evaluated for TLR9 single nucleotide polymorphisms − 1486 T/C (rs187084) and + 2848:G/A (rs352140) using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR).ResultsHealthy individuals had a significantly higher frequency of rs187084 AG and AG + GG genotypes than BD patients (p = 0.02 and p = 0.018; respectively). Of interest, healthy males had a significantly higher frequency of rs187084 AG + GG genotype and G allele than male BD patients (p = 0.035 and p = 0.045; respectively). However, rs187084 AG genotype and G allele frequencies were significantly higher in male patients with genital aphthous (p = 0.01 and p = 0.046; respectively). Furthermore, a significantly higher frequency of rs352140 CT and TT + CT genotypes was detected in healthy individuals than in BD patients (p = 0.01, and p = 0.032; respectively). Such results were also seen in healthy females than female patients (p = 0.001, and p = 0.004; respectively). Haplotype analysis revealed a significantly higher frequency of A-C and G-C haplotypes among patients and healthy subjects, respectively (p = 0.002 and p = 0.000; respectively).ConclusionOur data suggested that rs187084 AG and AG + GG genotypes and rs352140 CT and TT + CT genotypes protect Iranian individuals from BD but rs187084 AG genotype and G allele predispose male BD individuals to genital aphthous. However, additional studies are required to verify these results.

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.

How Can We Predict Disease Severity in Viral Infections?

How Can We Predict Disease Severity in Viral Infections?

The investigation of host genetic variants of toll-like receptor 7 and 8 in COVID-19

Toll-like receptors (TLRs) recognize infectious agents and play an important role in the innate immune system. Studies have suggested that TLR single nucleotide polymorphisms (SNPs) are associated with poor antiviral responses against SARS-CoV-2. Therefore, we aimed to investigate the relationship of TLR7 and TLR8 (SNPs) with COVID-19 disease prognosis. A total of 120 COVID-19 patients, 40 outpatients, 40 clinical ward patients and 40 intensive care unit (ICU) patients were included in the study. TLR7 (rs179009), TLR8-129 C/G (rs3764879) and TLR8 Met1Val (rs3764880) SNPs were genotyped using the PCR-RFLP method. In female patients, individuals carrying AG genotype and G allele for TLR8 Met1Val SNP were found at a higher frequency in patients hospitalized in the ICU than in patients followed in the clinical ward (p < 0.05). In terms of the other two SNPs, no significant difference was found between the groups in females. Furthermore, in male patients, A allele of TLR7 rs179009 SNP was at a higher frequency in patients who have at least one comorbidity than in patients who have no comorbidity (p < 0.05). Our results suggest that TLR8 Met1Val SNP is important in the COVID-19 disease severity in females. Furthermore, TLR7 rs179009 SNP is important in male patients in the presence of comorbid diseases.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study.

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud's arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (-1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position -1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Genetic variation in toll-like receptor 4 gene with primary antiphospholipid syndrome susceptibility: a cohort of Egyptian patients

BackgroundAs toll-like receptor 4 (TLR4) plays important roles in cellular immunity and TLR4 polymorphisms have been shown to be associated with susceptibility to a range of diseases, the present study aimed to investigate the association between TLR4 gene polymorphisms and the incidence of primary antiphospholipid syndrome (PAPS).MethodsTwo TLR4 single nucleotide polymorphisms (rs4986790 and rs4986791) were assessed in 110 subjects of Egyptian ethnicity, including 65 female patients with PAPS and 45 matched healthy controls, using polymerase chain reaction-restriction fragment length polymorphism. Results were verified using automated sequencing.ResultsThe homozygous wild-type (AA, aspartic acid) rs4986790 variant and (CC, threonine) rs4986791 variant were the predominant genotypes in the control and PAPS groups.ConclusionThe results of this preliminary study of TLR4 gene variants among patients with PAPS in an Egyptian population found no association between the rs4986790 and rs4986791 variants and susceptibility to PAPS.

Association of toll-like receptors polymorphisms with COPD risk in Chinese population.

Background: Previous studies have reported that the Toll-like receptors (TLRs) are related with the progress of chronic obstructive pulmonary disease (COPD). We aimed to explore the association of TLRs single nucleotide polymorphisms (SNPs) and COPD risk. Methods: 170 COPD patients and 181 healthy controls were enrolled in this case-control study. MassARRAY platform was used for genotyping seven tagging SNPs (TLR2: rs3804100, rs4696480, rs3804099; TLR3: rs3775290, rs3775291, rs5743305; TLR9: rs352140) of TLRs. The correlations between the SNPs and COPD risk were determined using logistic regression. Results: We found that the rs3775291 of TLR3 significant decreased the risk of COPD (TT versus CC: non-adjusted OR = 0.329, 95% CI = 0.123-0.879, p = 0.027). In the genetic models analysis, the rs3775291 was associated with a decreased effect of COPD based on the recessive model (TT versus CC/CT: non-adjusted OR = 0.377, 95% CI = 0.144-0.988p = 0.047). The rs4696480 of TLR2 gene was associated with a decreased risk of COPD after adjustment by age and gender (TA versus AA: adjusted OR = 0.606, 95% CI = 0.376-0.975, p = 0.039). Conclusion: Our study showed that genetic variants in TLRs were associated with risk of COPD. The rs3775291 and rs4696480 may act as a potential biomarker for predicting the risk of COPD in Chinese population.

Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma-A Single-Center Study.

Hepatocellular carcinoma (HCC) is the most common primary liver tumor leading to significant morbidity and mortality; its exact genetic background is largely unrecognized. Toll-like receptor-4 (TLR4) reacts with lipopolysaccharides, molecules found in the outer membrane of Gram-negative bacteria. In damaged liver, TLR4 expression is upregulated, leading to hepatic inflammation and injury. We tried to investigate the role of the two most common single-nucleotide polymorphisms (SNPs) of TLR4 in HCC-genesis. Aged > 18 years old, cirrhotic patients were included in this study. Exclusion criteria were non-HCC tumors and HIV co-infection. TLR4 SNPs association with HCC occurrence was the primary endpoint, and associations with all-cause and liver-related mortality, as well as time durations between diagnosis of cirrhosis and HCC development or death and diagnosis of HCC and death were secondary endpoints. A total of 52 out of 260 included patients had or developed HCC. TLR4 SNPs showed no correlation with primary or secondary endpoints, except for the shorter duration between HCC development and death in patients with TLR4 mutations. Overall, TLR4 SNPs showed no correlation with carcinogenesis or deaths in patients with liver cirrhosis; patients with TLR4 SNPs that developed HCC had lower survival rates, a finding that should be further evaluated.

Association of toll-like receptors single nucleotide polymorphisms with HBV and HCV infection: research status.

BackgroundHepatitis B virus (HBV) and hepatitis C virus (HCV) infections have become increasingly severe worldwide and are a threat to public health. There have been a number of studies conducted recently on the relationship of single nucleotide polymorphisms (SNPs) to innate immune receptor genes such as toll-like receptors (TLRs). Some literature suggests that SNPs of TLRs are associated with HBV and HCV infection. We summarized the role of TLRs gene polymorphisms associated with HBV and HCV infections and explored their possible mechanisms of action.MethodologyPubMed and Web of Science were used to perform the literature review. Related articles and references were identified and used to analyze the role of TLRs gene polymorphism in HBV and HCV infection.ResultsTLRs gene polymorphisms may have beneficial or detrimental effects in HBV and HCV infection, and some SNPs can affect disease progression or prognosis. They affect the disease state by altering gene expression or protein synthesis; however, the mechanism of action is not clearly understood.ConclusionsSingle nucleotide polymorphisms of TLRs play a role in HBV and HCV infection, but the mechanism of action still needs to be explored in future studies.

Toll-Like Receptors (TLRs) in Health and Disease: An Overview.

Toll-like receptors were discovered as proteins playing a crucial role in the dorsoventral patterning during embryonic development in the Drosophila melanogaster (D. melanogaster) almost 40years ago. Subsequently, further research also showed a role of the Toll protein or Toll receptor in the recognition of Gram-positive bacterial and fungal pathogens infecting D. melanogaster. In 1997, the human homolog was reported and the receptor was named the Toll-like receptor 4 (TLR4) that recognizes lipopolysaccharide (LPS) of the Gram-negative bacteria as a pathogen-associated molecular pattern (PAMP). Identification of TLR4 in humans filled the long existing gap in the field of infection and immunity, addressing the mystery surrounding the recognition of foreign pathogens/microbes by the immune system. It is now known that mammals (mice and humans) express 13 different TLRs that are expressed on the outer cell membrane or intracellularly, and which recognize different PAMPs or microbe-associated molecular patterns (MAMPs) and death/damage-associated molecular patterns (DAMPs) to initiate the protective immune response. However, their dysregulation generates profound and prolonged pro-inflammatory immune responses responsible for different inflammatory and immune-mediated diseases. This chapter provides an overview of TLRs in the control of the immune response, their association with different diseases, including TLR single nucleotide polymorphisms (SNPs), interactions with microRNAs (miRs), use in drug development and vaccine design, and expansion in neurosciences to include pain, addiction, metabolism, reproduction, and wound healing.

The Potential of Toll-Like Receptors to Modulate Avian Immune System: Exploring the Effects of Genetic Variants and Phytonutrients.

Toll-like receptors (TLRs) are pathogen recognition receptors, and primitive sources of innate immune response that also play key roles in the defense mechanism against infectious diseases. About 10 different TLRs have been discovered in chicken that recognize ligands and participate in TLR signaling pathways. Research findings related to TLRs revealed new approaches to understand the fundamental mechanisms of the immune system, patterns of resistance against diseases, and the role of TLR-specific pathways in nutrient metabolism in chicken. In particular, the uses of specific feed ingredients encourage molecular biologists to exploit the relationship between nutrients (including different phytochemicals) and TLRs to modulate immunity in chicken. Phytonutrients and prebiotics are noteworthy dietary components to promote immunity and the production of disease-resistant chicken. Supplementations of yeast-derived products have also been extensively studied to enhance innate immunity during the last decade. Such interventions pave the way to explore nutrigenomic approaches for healthy and profitable chicken production. Additionally, single-nucleotide polymorphisms in TLRs have shown potential association with few disease outbreaks in chickens. This review aimed to provide insights into the key roles of TLRs in the immune response and discuss the potential applications of these TLRs for genomic and nutritional interventions to improve health, and resistance against different fatal diseases in chicken.

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.

TLR4 896A/G and TLR9 1174G/A polymorphisms are associated with the risk of infectious mononucleosis

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and activate innate and adaptive immune responses. Single nucleotide polymorphisms (SNPs) within the TLR genes may influence host–pathogen interactions and can have an impact on the progression of infectious diseases. The present study aimed to investigate the genotype distribution of TLR2 (2029C/T, rs121917864; 2258G/A, rs5743708), TLR4 (896A/G, rs4986790), and TLR9 (− 1237T/C, rs5743836; − 1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) polymorphisms in 149 children and adolescents with infectious mononucleosis (IM) and 140 healthy individuals. The potential association of TLR SNPs with the clinical manifestations of EBV infection was also studied. The presence of TLR2, TLR4, and TLR9 SNPs was identified by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). EBV DNA loads were detected by quantitative real-time PCR assay. The TLR4 896 GG and the TLR9 1174 GA genotypes were associated with an increased risk of EBV-related IM in examined patients (p = 0.014 and p = 0.001, respectively). The heterozygous genotype of the TLR4 896A/G SNP was associated with an increased risk of elevated liver enzyme levels and leukocytosis (p < 0.05). Our preliminary study revealed that the TLR4 896A/G and the TLR9 1174G/A polymorphisms seem to be related to the course of acute EBV infection in children and adolescents.

Assessment of Toll Like receptor 2 Gene Polymorphism in Children with B Cell Defects and Respiratory Tract Infections

Abstract Acute respiratory tract infections are the most common illnesses in childhood. Respiratory defenses against infection involve a diverse and complex system. Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), recognize pathogen-associated molecular patterns (PAMPs), resulting in initiation of innate immune response and promotion of adaptive immunity. TLR single nucleotide polymorphisms (SNPs) impair the ability to respond properly to TLR ligands and increase susceptibility to infectious or inflammatory diseases. The aim of the work: To examine TLR2 Arginine 677Tryptophan (Arg 677Trp) and Arginine753Glutamine (Arg753Gln) gene polymorphisms in patients with recurrent or chronic respiratory tract infections with or without predominantly antibody deficiency (PAD). Subjects and methods: This cross-sectional case-control study included 30 patients with known PAD with/ or without respiratory tract infections, 20 non-PAD patients with recurrent chest infections and 20 age and sex-matched healthy controls. All children included in the study were subjected to full history taking, complete physical examination and laboratory investigations including CBC, serum immunoglobulins levels and genetic analysis of the TLR2 Arg677Trp and Arg753Gln polymorphisms. Computed tomography (CT) scan of the chest with contrast, pulmonary function tests (PFTs) and Bronchoalveolar lavage (BAL) fluid culture and sensitivity were performed to patients with recurrent and/or chronic chest infections. Results: There was a significant difference in the expression of Arg753Gln polymorphism (p 0.04) between PAD patients with and without recurrent chest infections. Patients with mutant or heterozygote state of this polymorphism had a short diagnosis lag (time elapsed between onset of symptoms and date of diagnosis). There was a significant relationship between this polymorphism and the duration of hospital admission (longer hospital stay in patients with mutant allele). A significant difference between non-PAD patients with recurrent chest infections and healthy controls regarding Arg 677 Trp polymorphism (p 0.04) was elicited. Conclusion: Our results suggest that Arg 677 Trp polymorphism could be a risk factor for increased susceptibility to recurrent and /or chronic respiratory tract infections in patients without PAD, while Arg753Gln polymorphism might be an additional risk factor for severe infections in PAD patients.

Association of TLR3 single nucleotide polymorphisms with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors

INTRODUCTION: The human T-lymphotropic virus type 1 (HTLV-1) has a single-stranded RNA genome and expresses specific proteins that have oncogenic potential. Approximately 15 to 20 million people worldwide have been infected by this virus. Changes in protein or gene expression are the effects of single nucleotide polymorphisms (SNPs) within the Toll-like receptor 3 (TLR3) gene. The function and efficacy of signal transduction also lead to modified immune responses. The present study aimed to investigate the association of SNPs within TLR3 (rs3775291 and rs3775296) with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors. METHODS: This study was performed on 100 HTLV-1-infected asymptomatic blood donors and 118 healthy blood donors. Genomic DNA from all participants was purified and then amplified using specific PCR primers. SNPs within TLR3 were evaluated using the restriction fragmentation length polymorphism technique, and the results were analyzed using SPSS software (version 22). RESULTS: The frequencies of the TLR3 (rs3775296) CC, CA, AA genotypes were 70%, 24%, and 6% in the patient group, and 50.8%, 44.9%, and 4.2% in the control group, respectively. There was a significant difference in the frequency distribution of TLR3 (rs3775296) genotypes and alleles, but not in the frequency distribution of TLR3 (rs3775291) genotypes between the patient and control groups. CONCLUSIONS: The TLR3 SNP rs3775296 was significantly associated with HTLV-1 infection and may be a protective factor against this viral infection.

Genetic Polymorphism of Toll-Like Receptor 4 Thr399Ile Variant in Iraqi Kurdish Population: Sulaymaniyah Province

Toll-like receptors (TLRs), encoded by innate immune genes, functions to detect microbial ligands. Studies found that polymorphisms in TLR genes among populations are associated with diseases. Among the classes of TLRs, TLR-4 is important for exploring bacterial lipopolysaccharide. TLR-4 Thre399Ile is one of the most important non-synonymous variant which varies among different background populations. Kurds, an ethnic population descended mainly from indigenous inhabitants of Zagros mountain survived for millennia, with nearly 40 million populations, are distributed in Iraq, Turkey, Iran and Syria. There are no studies on genetic variations of TLR4 in this population, particularly in Iraqi Kurdistan. The aim of this study is to find the percentage frequency of TLR4 Thr399Ile variant in Kurdish populations in Iraq, particularly in Sulaymaniyah province. The percentage of single nucleotide polymorphisms (SNPs) of the TLR4 gene was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results showed that the heterozygous variant of TLR4 Thr399Ile is 7.1% (n=85) in Sulaymaniyah populations. However, no homozygous mutant variant was found; this suggests that it is either absent or seldom among Kurds in the region. This study emphasises the perceptiveness of the TLR SNP in Sulaymaniyah populations that recommends future study for linking this genetic variation with both infectious and immunological diseases, in addition to historical, anthropological and archaeological studies.

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.

Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population.

BACKGROUNDToll-like receptors (TLRs) are the first line of host defense, and are involved in Helicobacter pylori (H. pylori) recognition and activation of both inflammatory and carcinogenic processes. The presence of single nucleotide polymorphisms (SNPs) in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer (GC). Among them, Toll-like receptor 9 (TLR9) polymorphisms have emerged with a risk factor of infectious diseases and cancer, however the studies are still inconclusive.AIMTo evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis, and its influence on mRNA expression.METHODSA case-control study was conducted to evaluate two TLR9 SNPs (TLR9-1237 TC-rs5743836 and TLR9-1486 CT-rs187084) in chronic gastritis (CG) and GC patients. A total of 609 DNA samples of peripheral blood [248 CG, 161 GC, and 200 samples from healthy individuals (C)] were genotyped by polymerase chain reaction-restriction fragment length polymorphism. All samples were tested for the H. pylori infection using Hpx1 and Hpx2 primers. Quantitative polymerase chain reaction by TaqMan® assay was used to quantify TLR9 mRNA from fresh gastric tissues (48 GC, 26 CG, and 14 C).RESULTSFor TLR9-1237, the TC + CC or CC genotypes were associated with a higher risk of GC than C [recessive model odds ratio (OR) = 5.01, 95% confidence interval (CI): 2.52-9.94, P < 0.0001], and the CG (recessive model OR =4.63; 95%CI: 2.44-8.79, P < 0.0001) groups. For TLR9-1486, an association between the CT + TT genotypes and increased risk of both GC (dominant model OR = 2.72, 95%CI: 1.57-4.72, P < 0.0001) and CG (dominant model OR = 1.79, 95%CI: 1.15-2.79, P = 0.0094) was observed when compared to the C group. Moreover, the presence of TLR9-1237 TC/CC + TLR9-1486 CC genotypes potentiate the risk for this neoplasm (OR = 18.57; 95%CI: 5.06-68.15, P < 0.0001). The TLR9 mRNA level was significantly higher in the GC group (RQ = 9.24, P < 0.0001) in relation to the CG group (RQ = 1.55, P = 0.0010) and normal mucosa (RQ = 1.0). When the samples were grouped according to the polymorphic genotypes and the presence of H. pylori infection, an influence of TLR9-1237 TC + CC polymorphic genotypes (P = 0.0083) and H. pylori infection (P < 0.0001) was observed on the upregulation of mRNA expression.CONCLUSIONOur findings show that TLR9 rs5743836 and rs187084 polymorphisms are associated with a higher risk of carcinogenesis gastric, and that TLR9 mRNA levels can be modulated by TLR9-1237 TC + CC variant genotypes and H. pylori infection.

Association Between Toll-Like Receptor 4 (TLR4) and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Genetic Variants and Clinical Progression of Huntington's Disease.

BackgroundAlthough Huntington's disease (HD) is caused by a single dominant gene, it is clear that there are genetic modifiers that may influence the age of onset and disease progression.ObjectivesWe sought to investigate whether new inflammation‐related genetic variants may contribute to the onset and progression of HD.MethodsWe first used postmortem brain material from patients at different stages of HD to look at the protein expression of toll‐like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells 2 (TREM2). We then genotyped the TREM2 R47H gene variant and 3 TLR4 single nucleotide polymorphisms in a large cohort of HD patients from the European Huntington's Disease Network REGISTRY.ResultsWe found an increase in the number of cells expressing TREM2 and TLR4 in postmortem brain samples from patients dying with HD. We also found that the TREM2 R47H gene variant was associated with changes in cognitive decline in the large cohort of HD patients, whereas 2 of 3 TLR4 single nucleotide polymorphisms assessed were associated with changes in motor progression in this same group.ConclusionsThese findings identify TREM2 and TLR4 as potential genetic modifiers for HD and suggest that inflammation influences disease progression in this condition. © 2019 International Parkinson and Movement Disorder Society