TLR4 Rs4986790 Research Articles

Evaluation of the Relationship between TLR1(RS4833095) Gene Polymorphism and Disease in Patients with Ulcerative Colitis in the Turkish Population

Background: Ulcerative Colitis is a multifactorial disease which is characterized by recurrent periods of inflammation in the mucosal layer of the colon. Toll-like receptors (TLRs) are a class of transmembrane pattern recognition receptors that play a key role in the induction of pro/anti-inflammatory genes and in the control of adaptive immune responses. In this study, we aimed to evaluate the relation between TLR1(rs4833095) single nucleotide polymorphism and ulcerative colitis. Methods: The study included 90 patients with ulcerative colitis and a healthy control group consisting of 90 people. Taken medical treatment, laboratory data, colonoscopy findings, extraintestinal manifestations of patients included in this study were recorded. TLR1(rs4833095) single nucleotide polymorphism was studied with RT-PCR methods. Results: There was no increased risk for ulcerative colitis in patients with ulcerative colitis who has TLR1(rs4833095) single nucleotide polymorphism in Turkish population (p>0.05). There was no association between TLR 1(rs4833095) single nucleotide polymorphism and the spread of the disease in the colon, severity of disease and treatment required for remission in our study(p>0.05). Conclusion: In the Turkish population, TLR1 (rs4833095) single nucleotide polymorphism was evaluated and no significant difference was found between the patients with ulcerative colitis and the control group.

Toxoplasma Gondii In Association with TLR4 Among Regular Hemodialysis Patients

Background: Hemodialysis patients can be considered immunocompromised as they have an increased risk of infections. The activity of Toll -like receptors in defense against infections was observed particularly for Toll like receptor4 molecule. Several single-nucleotide polymorphisms (SNPs) residing in genes encoding Toll -like receptors were reported as significant genetic modifications associated with infections. Aim: To determine the association between Toll- like receptors 4 polymorphisms and the susceptibility to infection with Toxoplasma gondii in hemodialysis patients. Materials and Methods: This case- control study was conducted on 150 patients with hemodialysis and 150 apparently healthy blood donors as control group, the samples were collected in the period from march 2021 to November 2021 from Al-Karama hospital and Al-Yarmouk Teaching Hospital. All patients were investigated for the presence of Toxoplasma gondii and Abs (IgG, IgM) by using ELISA technique and conformation by molecular technique (Real time-PCR). The selected SNPs in Toll- like receptors 4 were amplified by using conventional polymerase chain reaction PCR and then sequencing there polymorphism. Results: In the current study the comparison of median age between patients and controls was with no significant difference, while the laboratory tests revealed significant difference in median level of urea, creatinin , calcium , potassium ,albumin and hemoglobin, and insignificant difference for body mass index and sodium between studied groups. The ratio of females infected with Toxoplasma gondii was higher than infected males. The seropositive result in patients for Toxoplasma gondii - IgG and IgM was 15 and 6 respectively while 19 patients were positive by PCR. However in control group there were 8 patients seropositive for IgG and positive in PCR results while the results of IgM and PCR were negative for all control group. The Polymerase chain reaction (PCR) products of Toll- like receptors 4 genes were subjected for direct sequencing by using Bio edit software. And the resultant sequences were compared with reference sequences in NCBI. The analysis of TLR-4 rs4986790 genotypes were 24(80%) AA and 6(20%) AG in patients while 6 (60%) AA and 4(40%) AG in controls with insignificant difference, while the analysis of TLR-4 rs4986791 genotypes were 24(80%) CC and 6 (20%) CT in patients while 6 (60%) CC and 4(40%) CT in controls with insignificant difference. Conclusion: There was no significant association of Toxoplasma gondii with TLR4 genotypes of rs4986790 and rs4986791 SNPs in hemodialysis patients.

Influence of polymorphisms on the phenotype of TLR1, TLR4 and TLR9 genes and their association with cervical cancer: Bioinformatics prediction analysis and a case-control study

Susceptibility to cervical cancer has been associated with Toll-like receptors (TLRs), which is an important component of innate immunity. According to previous studies, polymorphisms in TLRs genes can affect immune response pathways and lead to the development of cervical cancer. The present study aims to evaluate the functionality of polymorphisms in TLR1, TLR4 and TLR9 genes and their associations with cervical cancer. To identify the functionality of polymorphisms, we used the following tools: MUpro, ChimeraX, SNP2TFBS and GTEx. A case-control study including 57 cases (11 High-grade Intraepithelial Lesion - HSIL and 46 cervical cancer) and 67 clinically healthy controls was conducted in the Brazilian population. Polymorphisms genotyping was performed by real-time PCR, using TaqMan probes, using the allelic discrimination method. Bioinformatics prediction showed that the TLR1 rs4833095 [NM_003263.4 (TLR1):c.743T>C (p.Asn248Ser)] and TLR4 rs4986790 [NM_138554.5 (TLR4):c.896A>G (p.Asp299Gly)] polymorphisms alter the structure and stability of their respective proteins. TLR9 rs187084 [NM_017442.3(TLR9):c.-1486A>G] polymorphism seems to affect the THAP1 binding site and modify gene expression. In the case-control study, the c.743TC heterozygous genotype of the rs4833095 SNP in the TLR1 gene was associated with an increased risk for HSIL/cervical cancer. No association of TLR4 rs4986790 and TLR9 rs187084 SNPs with HSIL/cervical cancer was found in the studied population. Allelic combination CAG (rs4833095/ rs4986790/ rs187084) increased the risk of cervical cancer. In conclusion, the present study identified that polymorphisms in TLRs genes can affect the phenotype of their respective genes and contribute to the development of HSIL or cervical cancer.

Association of the Single Nucleotide Polymorphism 19216T/C in the TLR2 Gene (rs3804099) with Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii Infection Among Lebanese Children.

Toll-like receptors (TLRs), particularly the TLR2, take part in the elicitation of immune responses against Entamoeba histolytica. This study aimed to investigate the relationship between a specific polymorphism called rs3804099 in the TLR2 gene and E. histolytica/E. dispar/E. moshkovskii infection among Lebanese children. A case-control study encompassed 180 participants including 68 children with amebiasis and 112 matched controls. Blood samples were collected, and genomic DNA was extracted using the classical proteinase K digestion and phenol-chloroform extraction method. The variant rs3804099 was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction. The accuracy of the genotyping was supported by sequencing 5% of samples. The TLR2 rs3804099 polymorphism was identified in the studied population, and the observed genotypic distributions were consistent with Hardy-Weinberg equilibrium (P > 0.05). The frequency of the rare CC genotype was significantly higher in patients compared to the noninfected group (P < 0.01). In controls, the homozygous TT genotype was less frequent than the heterozygous CT genotype. The rare CC genotype was associated with a higher risk of amebiasis among children (odds ratios = 3.27, P = 0.002). These findings provide evidence supporting the association between the rs3804099 SNP in the TLR2 gene and E. histolytica/E. dispar/E. moshkovskii infection among Lebanese children.

Polymorphisms in the genes encoding RLR and TLR3 and CMV DNAemia in subjects coinfected with human immunodeficiency virus and cytomegalovirus

Cytomegalovirus (CMV) is a pathogen that is common worldwide and is often present in individuals infected with human immunodeficiency virus (HIV). Pattern recognition receptors (PRRs) are host sensors that activate the immune response against infectious agents. However, it is unclear whether PRR single-nucleotide polymorphisms (SNPs) are associated with the occurrence of CMV DNAemia in subjects coinfected with HIV and CMV. HIV/CMV-coinfected patients with and without CMV DNAemia were recruited for this study. The DDX58 rs10813831 and IFIH1 (rs3747517 and rs1990760) polymorphisms were genotyped using the TaqMan Allelic Discrimination Assay, whereas the DDX58 rs12006123 and TLR3 (rs3775291 and rs3775296) SNPs were analyzed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. A mutation present in at least one allele of the DDX58 rs12006123 SNP occurred at least two times more frequently in HIV/CMV-coinfected patients with CMV DNAemia than in coinfected subjects without CMV DNAemia (OR, 2.50; 95% CI, 1.33–4.68; p = 0.004, in the dominant model). A higher level of CMV DNAemia was observed in subjects who had the heterozygous (GA) or homozygous recessive (AA) genotype for the DDX58 rs12006123 SNP compared with those who had the wild-type (GG) genotype (p = 0.0003). Moreover, in subjects with a mutation detected in at least one allele of the DDX58 rs12006123 SNP, a lower serum IFN-β concentration was found compared with those who had a wild-type (GG) genotype for this polymorphism (p = 0.024). The DDX58 rs12006123 SNP is associated with CMV DNAemia in HIV/CMV-coinfected patients.

Epidemiological and genetic aspects of pulmonary tuberculosis in Kazakhstan

ObjectiveTuberculosis is a major health problem in many countries, including Kazakhstan. Host genetics can affect TB risk, and epidemiological and social factors may contribute to disease progression. Due to the high incidence of pulmonary tuberculosis in the country, our research aimed to study the epidemiological and genetic aspects of pulmonary tuberculosis in Kazakhstan. Material and methods1026 participants of Central Asian origin were recruited in the study: 342 individuals diagnosed with active PTB, 342 household contacts, and 342 controls without a family history of TB. Genetic polymorphisms of selected genes were determined by real-time polymerase chain reaction. The association between the risk of pulmonary TB and polymorphisms was evaluated using logistic regression and assessed with the ORs and their corresponding 95 % CIs, and the significance level was determined as p < 0.05. ResultsEpidemiological data revealed that underweight BMI (χ² = 89.97, p < 0.001), employment (χ² = 39.28, p < 0.001), and diabetes (χ² = 12.38, p < 0.001) showed a significant association with PTB. A/T polymorphism of the IFG gene showed a lower risk, and A/A polymorphism showed an increased risk of susceptibility to TB. A/A polymorphism of the IFG gene was associated with an almost 3-fold increased risk of PTB, and A/T polymorphism of the IFG gene was associated with a decreased risk of PTB (OR = 0.67, 95 % CI = 0.49–0.92, p = 0.01). The analysis revealed a decreased risk of PTB for A/A polymorphism of the VDR ApaI (OR = 0.67, 95 % CI = 0.46–0.97, p < 0.05). A/A polymorphism of the TLR8 gene was associated with a 1.5-fold increased risk of PTB (OR = 1.53, 95 % CI = 1.00–2.33, p < 0.05). ConclusionResults showed that gender, employment, underweight BMI and diabetes are associated with PTB incidence in our study cohort. The A/A genotype of the IFG (rs2430561) and an A/A genotype of the TLR8 (rs3764880) genes were associated with an increased risk of PTB. A/T polymorphism of the IFG (rs2430561) and A/A polymorphism of the VDR ApaI were associated with a decreased risk of PTB.

Assessing risks of secondary immunodeficiency in children with aluminum contamination in biological media and polymorphism of the cell death gene FAS rs1159120 and the antigen-recognizing gene of the toll-like receptor TLR4 rs1927911

Secondary immunodeficiency remains an incompletely understood medical problem, and despite a significant number of international and scientific studies, there is no complete picture of the causes and consequences of this pathology. Metal cations have been proven to participate in the formation of acquired immunodeficiency. In particular, aluminum properties as an immune suppressor have been established and its targets in the body have been identified in case aluminum was present in biological media. However, no evaluations have been accomplished so far as regards the role of specific point genetic changes, that is, polymorphisms in the genes of immune system compartments that determine the risk of negative effects caused by contamination with metal cations, including aluminum. It is quite relevant to search and substantiate immunogenetic markers to create an indicator system for diagnostics and prevention of secondary immunodeficiency states in children associated with aluminum contamination in biological media. We examined 97 preschool children exposed to elevated levels of airborne aluminum (in an area influenced by a metallurgic production). The study groups were divided depending on either presence or absence of secondary immunodeficiency as immune system pathology (common variable immunodeficiency D83). Several markers of the immune system were evaluated: aluminum-specific IgG, CD3+, CD4+, CD8+, CD127-, CD95+, CD284+, and phagocytic activity; we also evaluated polymorphism of TLR4 A8595G (rs1927911) and FAS C14405T (rs1159120) genes of innate and acquired immunity. According to the results obtained by examining biological media composition, children with secondary immunodeficiency had 1.8 times higher aluminum levels in urine (0.0095 ± 0.0014 vs. 0.0054 ± 0.0009 mg/dm3, reference range &lt; 0.0075 mg/dm3) as opposed to their conditionally healthy peers. We established an authentic inverse dependence between the expression level of the main CD clusters (CD3+: r = -0.38; CD4+: r = -0.39; CD8+: r = -0.26) as well as indicators of phagocytic activity (r = -0.22–0.23) and the level of aluminum contamination in biological media (urine). Expression of T-mature lymphocyte clusters was found to be inhibited by 1.3–3.1 times (including T-helper, effector T-lymphocytes, NK-killers, regulatory lymphocytes) and we also detected some changes in expression of specific immunoglobulin of IgG class to aluminum. All this results in an unacceptable level of relative risk (RR = 1.23–1.63) of developing secondary immunodeficiency against increased frequency of allele C and genotype CC of FAS gene (rs1159120) by 1.2 and 1.5 times respectively, as well as minor allele G of TLR4 gene (rs1927911) by 1.8 times relative to the comparison group (OR = 4.05; CI: 1.41–11.59; p = 0.006; RR = 1.23; CI: 1.02–1.48) and (OR = 2.01; CI: 1.04–3.91; p = 0.037; RR = 1.64; CI:1.46–1.94). Toll-dependent and FAS-dependent mechanism of this risk is associated with aluminum contamination. It is recommended to use a combination of immune and genetic markers as indicator ones when evaluating the immune system state, in order to prevent the risk (RR = 1.23–1.63) of secondary immunodeficiency associated with aluminum contamination in biological media.

The role of TLR4 rs1927911 gene polymorphism and toll-like receptor expression in the formation of allergy and its features in children under conditions of destabilization of the environment

Introduction. Anthropogenic chemical environmental factors modify the immune response, participate in the formation of immunodeficiency in children, and contribute to the occurrence of pathological conditions associated with allergies and autoimmunity. Purpose of the study. To analyze changes in the immunological and genetic profile in the children population living in an industrial area and suffering from allergic diseases. Materials and methods. An immunological and genetic examination was carried out on one hundred forty six 7–9 years children, permanently residing in the zone affected by emissions of a large non-ferrous metallurgy enterprise. The number of subpopulations and populations of lymphocytes (CD25, CD284) was determined by the cytofluorometric method. The content of IgE specific to nickel and formaldehyde was studied using the allergosorbent method. TLR4 rs1927911 and GSTP1 rs1695 gene polymorphisms were determined by real-time PCR. Results. There was obtained data indicating an imbalance of CD284 cell differentiation clusters, general IgE by 1.8 times and tobacco-specific by more than 2 times, as well as IgE specific to nickel and formaldehyde by 1.7 and 1.8 times, respectively. In children with allergy pathology the frequency of the A allele of the TLR4 rs1927911 gene has been established to be significantly increased. Research limitations. Children living near large industrial sources for at least three years. Conclusion. Children with allergies living in the zone influenced by emissions from non-ferrous metallurgy enterprises have an increased expression of cell clusters and excessive sensitization to haptens. Allergic manifestations are associated with polymorphism of the detoxification gene GSTP1 and the congenital atopy gene TLR4.

Association between Toll-like receptor 2 rs4696483 and rs1898830 polymorphisms and the risk of triple-negative breast cancer

PurposeBreast cancer (BC) is heterogeneous in clinical manifestation, of which the triple-negative (TNBC) subtype is the most aggressive. This study examines the associations between Toll-Like Receptor (TLR)-2 polymorphisms and the susceptibility to BC and TNBC. MethodsGenotyping of TLR-2 rs1898830 and rs4696483 polymorphisms was done by real-time PCR in 488 women with BC (130 TNBC, 358 non-TNBC) and 476 cancer-free control women. ResultsThe minor allele frequency (MAF) of rs4696483 was significantly lower in BC cases compared to controls, and significantly lower frequencies of rs4696483 C/T and higher frequencies of rs1898830 G/G genotypes were seen in BC cases. Significantly higher MAF of rs4696483 and higher C/T and T/T rs4696483 genotypes frequencies were seen in TNBC than in non-TNBC cases. Considering the prevalent AC haplotype as a reference, 2-locus TLR-2 haplotype analysis did not identify any 2-locus TLR-2 haplotype associated with an altered risk of BC or TNBC. Positive associations of rs1898830 and rs4966483 were seen with the histological type in TNBC and negatively with distant metastasis and HR status in TNBC and non-TNBC rs1898830 carriers. In addition, rs4696483 was positively correlated with hormonotherapy and surgery in non-TNBC cases, while rs1898830 was negatively associated with hormonotherapy. Furthermore, rs1898830 was negatively and positively correlated with BMI in TNBC and TNBC cases, respectively, but positively with Ki-67 status. ConclusionsOur study highlights the association between TLR-2 genetic polymorphisms and BC and TNBC susceptibility, suggesting these variants' diagnostic/prognostic capacity in BC patients and patient subgroups.

TLR2 and TLR4 Polymorphisms Are Not Associated with Dental Caries in Polish Children.

The aim of the present study was to analyze the association of the TLR2 (Toll-like receptor 2 gene) 2258G>A (rs5743708), TLR4 (Toll-like receptor 4 gene) 896A>G (rs4986790), and TLR4 1196C>T (rs4986791) polymorphisms with dental caries in Polish children. The participants, 261 15-year-old children, were divided into two groups: 82 cases (i.e., children with DMFT (Decayed, Missing, and Filled Teeth) index >5, having either moderate or high caries experience, assigned as the "higher" caries experience group) and 179 controls (i.e., children with DMFT ≤ 5, having either low or very low caries experience, assigned as the "lower" caries experience group). Genomic DNA was isolated from buccal swabs, and genotyping was determined by means of real-time PCR (polymerase chain reaction). There were no significant differences in the genotype or allele distributions in all tested SNPs (single nucleotide polymorphisms) between children with "higher" caries experience and those with "lower" caries experience. TLR4 haplotype frequencies did not differ significantly between cases and controls. In an additional analysis with another case definition applied (subjects with DMFT ≥ 1 were assigned as "cases", whereas children with DMFT = 0 were assigned as "controls"), no significant differences in the TLR2 and TLR4 genotype, allele frequencies, and TLR4 haplotype frequencies were found between the case and the control groups. The results of the present study broaden our knowledge on the potential genetic factors that might affect caries risk and suggest that TLR2 rs5743708 and TLR4 rs4986790 and rs4986791 SNPs are not associated with dental caries susceptibility in Polish children.

Genetic variation of TLR3 gene is associated with the outcome of hepatitis b infection in mauritanian patients: case control study

BackgroundToll-Like receptors (TLRs) play an important role in the immune response during hepatitis B virus (HBV) infection. In this study, we evaluated the association between two SNP variants (TLR3 rs3775290 and TLR4 rs4986790) and susceptibility to chronic HBV infection in Mauritania.Subjects and methods: A total of 188 subjects were recruited for this study: 102 chronically infected patients and 86 individuals with spontaneously resolved HBV infection who were considered controls. Targeted PCR products were sequenced using Sanger sequencing.ResultsWe found that TLR3 rs3775290 was significantly more frequent in patients with chronic HBV than in the control population (p = 0.03). However, no association was found between the TLR4 rs3775290 polymorphism and chronic infection.ConclusionOur results suggest that the TLR3 rs3775290 polymorphism may be a risk factor for susceptibility to chronic HBV infection in the Mauritanian population.

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects

The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7–2.3) versus 1.0 (0.5–1.9) μM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20–81) versus 29 (14–60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22–0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02–0.63)) and IL6R rs8192284 carrier (0.55 (0.34–0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2–9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.

Variations in the interferon and TLR3 genes may be associated with susceptibility to systemic lupus erythematosus and its clinical presentation

The study aimed to explore the pontential impact of 10 polymorphisms within IFN-α, IFN-β1, IFN-γ and TLR3 genes on SLE phenotype and susceptibility and to study the relationship between specific genotypes and clinics. Whole blood samples from SLE patients and healthy controls was obtained. DNA was extracted from the peripheral blood by the QIAamp DNA Blood Mini Kit (Qiagen). The quality and quantity of isolated DNA was estimated by the Quawell Q5000 spectrophotometer. We genotyped SLE patients and healthy subjects using real-time PCR (QuantStudio 5 thermocycler). The study suggests that IFN-γ rs2069705, IFN-γ rs2069718 and IFN-α rs3758236 polymorphisms have a protective role in SLE. We observed relations between TLR3 rs3775292, IFN-β1 rs7873167, IFN-γ rs2069705, TLR3 rs3775291 and TLR3 rs5743305 polymorphisms and clinical picture of SLE patients. We found associations between the IFN-α rs3758236, IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493 and IFN-β1 rs10964831 polymorphisms and the clinical manifestation of the SLE and/or its comorbidities. We perceived links between IFN-γ rs2069705, IFN-γ rs2069718, IFN-γ rs1861493, TLR3 rs3775291, TLR3 rs3775292 and TLR3 rs5743305 polymorphisms and the occurrence of autoantibodies. Our study presented the relationship between IFN and TLR gene polymorphisms with SLE susceptibility, phenotype and autoantibodies profile. This study propose that polymorphisms within interferons and TLR3 genes can be engaged in the SLE pathogenesis and course.

Genetic polymorphisms of TLR1, TLR2, TLR3 and TLR4 in patients with recurrent or severe infections.

Toll-like receptors (TLRs) play an important role in innate immunity. Previous studies have shown that single nucleotide polymorphisms (SNPs) in the genes coding for these innate immune molecules can affect susceptibility to and the outcome of certain diseases. The aim of the present study was to examine the clinical relevance of well-studied TLR1-4 SNPs in individuals who are prone to infections. Four functional SNPs, TLR1 rs5743618 (1805C>A, Ser602Ile), TLR2 rs5743708 (2258G>A, Arg753Gln), TLR3 rs3775291 (1234C>T, Leu412Phe) and TLR4 rs4986790 (896A>G, Asp299Gly), were analysed in 155 patients with recurrent respiratory infections (n=84), severe infections (n=15) or common variable immunodeficiency (n=56), and in 262 healthy controls, using the High Resolution Melting Analysis method. Polymorphisms of TLR2 rs5743708 (odds ratio [OR] 3.16; 95% confidence interval [CI] 1.45-6.83, p=.004, ap=.016) and TLR4 rs4986790 (OR 1.8; 95% CI 1.05-3.12, p=.028, ap=.112) were more frequent in patients with recurrent or severe infections than in controls. Interestingly, seven patients were found to carry both variant genotypes of TLR2 and TLR4, whereas none of the control group carried such genotypes (p≤.0001). Moreover, TLR2 polymorphism was associated with increased risk for acute otitis media episodes (OR, 3.02; 95% CI 1.41-6.47; p=.012). This study indicates that children and adults who are more prone to recurrent or severe respiratory infections carry one or both variant types of TLR2 and TLR4 more often than control subjects. Genetic variations of TLRs help explain why some children are more susceptible to respiratory infections.

FURIN, IFNL4, and TLR2 gene polymorphisms in relation to COVID-19 severity: a case-control study in Egyptian patients.

A wide range of clinical manifestations and outcomes, including liver injury, have been reported in COVID-19 patients. We investigated the association of three substantial gene polymorphisms (FURIN, IFNL4, and TLR2) with COVID-19 disease susceptibility and severity to help predict prognosis. 150 adult COVID-19-assured cases were categorized as follows: 78 patients with a non-severe presentation, 39 patients with severe disease, and 33 critically ill patients. In addition, 74 healthy controls were included. Clinical and laboratory evaluations were carried out, including complete and differential blood counts, D-dimer, lactate dehydrogenase (LDH), C-reactive protein (CRP), procalcitonin, ferritin, interleukin-6 (Il-6), and liver and kidney functions. FURIN (rs6226), IFNL4 (rs12979860), and TLR2 (rs3804099) genotyping allelic discrimination assays were conducted using real-time PCR. The FURIN, IFNL4, and TLR2 genotypes and their alleles differed significantly between COVID-19 patients and controls, as well as between patients with severe or critical illness and those with a non-severe presentation. According to a multivariable regression analysis, FURIN (C/T + T/T) and TLR2 (T/C + C/C) mutants were associated with COVID-19 susceptibility, with odds ratios of 3.293 and 2.839, respectively. FURIN C/C and IFNL4 T/T mutants were significantly linked to severe and critical illnesses. Multivariate regression analysis showed that FURIN (G/C + C/C) genotypes and IFNL4 T/T homozygosity were independent risk factors associated with increased mortality. FURIN, IFNL4, and TLR2 gene variants are associated with the risk of COVID-19 occurrence as well as increased severity and poor outcomes in Egyptian patients.

Association of TLR4 gene rs4986790 and rs4986791 polymorphisms with asthma susceptibility: meta-analysis and trial sequential analysis.

The current understanding of the correlation between TLR4 gene (toll-like receptor 4) rs4986790 and rs4986791 polymorphisms and asthma susceptibility is inconclusive, with studies and populations yielding conflicting results. Evaluate this relationship using meta-analysis and trial sequential analysis (TSA). Databases were systematically queried for relevant articles from the establishment of the database to 19 June 2023 adhering to predefined inclusion and exclusion criteria. Two authors independently conducted screening, data extraction, and quality evaluation. Meta-analysis and TSA were carried out using RevMan 5.4, StataMP 17.0, and TSA 0.9.5.10 Beta, with α=0.05. Subgroup analyses were conducted based on racial demographics. A sensitivity analysis was conducted employing a one-by-one exclusion method. Publication bias was assessed using the Begg and Egger tests. Association of asthma susceptibility with TLR4 gene rs4986790 and rs4986791 polymorphisms. 23 articles included 22 studies on the rs4986790 polymorphism and 11 studies on the rs4986791 polymorphism on the TLR4 gene. Out of 692 studies screened, 23 met the inclusion criteria. While the overall meta-analysis showed no significant association between the TLR4 rs4986790 polymorphism and asthma susceptibility, subgroup analysis revealed a significant link in the Caucasian population. A significant association was noted in the meta-analysis, particularly among Asian populations, on the rs4986791 polymorphism. The sensitivity analysis indicated that the meta-analysis results were relatively stable. Publication bias analysis revealed minimal influence from publication bias. However, TSA was underscored by the necessity for additional original studies to further validate specific outcomes. Our study underscores the ethnicity-specific impact on the relationship between TLR4 polymorphisms and asthma susceptibility. While the overall findings for rs4986790 were not significant, the association with the Caucasian population merits further investigation. Furthermore, rs4986791 demonstrated a significant correlation with asthma susceptibility, specifically among Asian populations. Our study predominantly examined the rs4986790 and rs4986791 polymorphisms, overlooking the potential influence of other genetic variants within TLR4.

Genetic Diversity of Plasmodium vivax Surface Ookinete Protein Pvs25 and Host Genes in Individuals Living along the Thai–Myanmar Border and Their Relationships with Parasite Density

Plasmodium vivax (Pv) accounts for over 50% of malaria cases in Latin America and Asia. Despite a significant reduction in Pv transmission in Thailand, the parasite remains endemic to the border areas. This study aimed to investigate the genetic diversity of the parasites and the host factors, as well as their relation to parasite density in Pvisolates, along the Thai–Myanmar border. Genetic variations in Pv markers, specifically the ookinete surface protein Pvs25, and host genes, including Toll-like receptor 6 (TLR6), TLR9, TIR Domain-containing adaptor protein (TIRAP), Toll-interacting protein (TOLLIP), Duffy antigen receptor for chemokines (DARC), and intercellular adhesion molecule 1 (ICAM-1), were investigated using polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP). A total of 548 PCR-positive Pv samples collected from Tak and Kanchanaburi provinces during two periods (2006–2007 and 2014–2016) were included in the study. Pvs25 exhibited four haplotypes, with H1 (EGTKV) being the most prevalent in both provinces. Kanchanaburi isolates exhibited greater genetic diversity than Tak isolates. No significant deviations from neutrality were observed for Pvs25 in either area. ICAM-1 and TOLLIP s3750920 heterozygous carriers had greater median parasite densities than homozygous mutants. The TLR9 rs187084 T genotype had a significantly higher parasite density than the non-T genotype. The findings underscore the significant association between the rs3750920 C/T, rs5498 A/G, and rs187084 T genotypes and high parasite density in patients infected with Pv, highlighting their potentially critical role in malaria susceptibility.

Prognostic significance of &lt;I&gt;TLR3&lt;/I&gt; and &lt;I&gt;TLR9&lt;/I&gt; gene polymorphism in assessing the severity of COVID-19

Objective: to study polymorphic variants of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with COVID-19 depending on the severity of the disease and their significance for determining the risk of severe course of COVID-19.Materials and Methods: genetic analysis of polymorphism of TLR3 (rs3775291) and TLR9 genes (rs352140) was performed in 164 patients with COVID-19, who were divided by degree of severity into three groups: Group 1 with mild, Group 2 with moderate and Group 3 with severe and extremely severe degrees of severity. The control group consisted of 40 healthy donors. Statistical processing of the obtained results was carried out using STATISTICA 12.0 programs (Stat Soft, USA). To assess the difference of groups by qualitative characteristics, the χ2 criterion with Yates correction was used, and in case of violation of its conditions, the χ2 criterion was applied. Yates correction, and if the conditions of its applicability were violated, the two-sided Fisher’s two-sided criterion (RF). The difference between the groups was considered statistically significant at р&lt;0,05. The strength of associations was evaluated in the values of the odds ratio index odds ratio (OR) and 95% confidence interval.&gt; ˂ 0,05. The strength of associations was evaluated in the values of the odds ratio index odds ratio (OR) and 95% confidence interval.Results: the frequency of the ST genotype was significantly higher and the frequency of the TT genotype of the rs3775291 allele of the TLR3 gene was significantly lower in patients with the manifest form of COVID-19 compared with the control group. Frequency analysis of TLR9 (rs352140) in COVID-19 patients showed significantly higher values of the ST genotype and lower values of the CC genotype compared to healthy individuals. Comparative analysis between groups of hospitalized patients depending on severity revealed higher frequency of ST genotype and lower frequency of TT genotype of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with severe and extremely severe condition.Conclusion: reliable differences in the frequency of occurrence of genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with the manifest form of COVID-19 compared to healthy people were revealed. The analysis of nucleotide sequence variants of the studied genes in hospitalized patients depending on the degree of severity also showed significant differences in the frequency of genotypes. Thus, in patients with severe and extremely severe COVID-19, a significant difference in the frequency of occurrence of ST and TT genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes was revealed compared to patients with mild and moderate COVID-19, which may further have prognostic value in assessing the severity of the disease.

Deciphering the role of TLR3 polymorphisms in oral squamous cell carcinoma pathogenesis: A case-control study.

Oral squamous cell carcinoma (OSCC) poses a significant global health burden, particularly prevalent in regions like India. Despite advancements in diagnostics, early detection of OSCC remains challenging, necessitating novel diagnostic modalities. Toll-like receptors (TLRs) and their polymorphisms have emerged as potential contributors to OSCC pathogenesis. This retrospective case-control study examined 120 individuals, including 60 OSCC cases and 60 healthy controls. Genotyping of TLR3 single-nucleotide polymorphisms (SNPs) rs3775290 and rs3775291 was conducted using TaqMan allelic discrimination real-time polymerase chain reaction. Functional consequence analysis and TLR3 expression profiling were performed to elucidate their role in OSCC pathogenesis. Significant associations were observed between TLR3 SNPs and OSCC susceptibility, particularly at loci rs3775290 and rs3775291. Functional consequence analysis revealed pathogenic mutations in TLR3 genes, potentially affecting protein structure and function. TLR3 overexpression was detected in OSCC lesions, implicating its involvement in disease progression. TLR3 polymorphisms play a pivotal role in OSCC pathogenesis, offering potential biomarkers for diagnosis and prognosis. Targeting TLR3-mediated pathways may hold promise in personalised OSCC management. Further research is warranted to elucidate the precise mechanisms underlying TLR3-mediated carcinogenesis in OSCC, facilitating the development of tailored therapeutic strategies.

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.