TLR4 Gene Polymorphisms Research Articles

TLR4 gene polymorphism associated with lifetime cigarette smoking in bipolar disorder

Bipolar disorder (BD) is associated with an increased risk of tobacco dependence, the leading addictive substance worldwide. Toll-like receptor 4, a sensor of pathogens and of products of cellular stress and damage, is a major innate immune molecule and logical candidate gene for tobacco dependence in BD because (i) the involvement of TLR4 molecules in several substance use disorders has been suggested, (ii) and the association between the TLR4 gene and BD. We analysed herein the potential association between six TLR4 polymorphisms and lifetime tobacco smoking in 514 BD patients. Significant association between tobacco smoking and rs10759932 was found (genotype, Cochrane Armitage trend test, p=0.008, pcorrected=0.040 and alleles, p=0.008; pcorrected=0.040), where the C minor allele is associated with a protective effect, even after adjusting for confounding factors (OR=1.54 [1.04–2.30], p=0.03). Our results suggest that TLR4 gene polymorphism may act as an intermediate factor for the association between tobacco smoking addiction and BD.

Polymorphisms of TLR4 Gene and Its Association With Genetic Resistance to Salmonella Enteritidis Infection in Fayoumi Breed and Hy-line Strain in Egypt

The aim of this study is to screen for genetic resistance to different doses of salmonella infection and its possible association with polymorphisms in exon 1 and 2 of TLR4 in Fayoumi breed and Hy-line strain of chickens. Two experiments was done, first one for measuring the variation of TLR4 -exon 1 and exon 2 of different genotypes of chicken under study and resistance to salmonella enteritidis. This study include 100 birds of each breeds, were infected orally with LD50 (108 cfu) salmonella enteritidis at age of two weeks and was divided into two groups (susceptible and resistance). TLR4 gene was genotyped with PCR-RFLP, The genotyping results on exon 1 (596 bp) by Taq1 restriction enzyme showed that the BB genotypes is more resistance to infection in the Fayoumi breed and also the AB genotypes is more resistance to infection in the Hy-line strain. Also The genotyping result on exon 2 (793 bp) by EcoR1 restriction enzyme showed only one genotype BB in Fayoumi breed and The frequency of AB genotypes is more resistant to infection than BB genotypes in Hy-line strain. The second experiment to evaluate the variation in immune response to the different genotypes of TLR4 -exon 1 and exon 2 this study include 100 birds of each breeds were infected with (5× 107 cfu) salmonella enteritidis and according to Elisa results the chickens devided into two groups (high and low immune response). The genotyping result on exon 1 (596 bp) by Taq1 restriction enzyme showed that the AB genotypes produce high immune response in both Fayoumi breed and Hy-line strain so can be used as a genetic marker for increase the immune response in chicks under study. Also The genotyping result on exon 2 (793 bp) by EcoR1 restriction enzyme showed only one genotype BB genotypes in Fayoumi breed and Hy-line strain.

Toll-Like Receptors in the Progression of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cause of chronic kidney disease. The intriguing role of innate immune system and inflammation become a target for potential therapeutic approach to slow progression. When toll-like receptors (TLRs) signaling and their receptors activate, they start a cascade of intracellular signaling that induces the production of the inflammatory cytokines and chemokines. Thus, we aim to investigate the association of TLRs between progression of ADPKD. Ninety ADPKD patients and ninety matched controls were enrolled this prospective study and were followed during 3 years. TLR-2 and TLR-4 gene polymorphisms and expressions were measured. Hypertension was diagnosed with ambulatory blood pressure monitoring. Rapid progression was defined as sustained decline in estimated glomerular filtration rate (eGFR) of more than 5 mL/min per 1.73 m2 per year. TLR-4Asp299Gly polymorphisms were significantly different between patient and control group (P < 0.05). Also, TLR-2 and TLR-4 gene expressions were significantly different between the ADPKD patients and the control subjects (P < 0.05). The expression levels of both TLR-2 and TLR-4 were found to be higher in the rapid progression groups comparing the slow progression group (P < 0.05). TLR-2 gene expression, hypertension and uric acid were found to be independent risk factors in identifying rapid progression in ADPKD patients. TLR-2 and TLR-4 gene expressions are associated with rapid progression in ADPKD patients. TLRs may play a role in the progression of ADPKD.

THE RISK OF EARLY LIVER ALLOGRAFT DYSFUNCTION IS ASSOCIATED WITH THE TLR-4 GENE GENOTYPE IN THE RS913930 SEQUENCE AND IS IMPLEMENTED VIA HMGB1 NUCLEAR PROTEIN, KUPFFER CELLS AND IL-23 ACTIVATION

Aim.To evaluate the associations of genotypes of clinically relevant nucleotides rs11536865, rs913930 and rs5030717 of the TLR-4 gene with the risk of development and severity of early allograft dysfunction after liver transplantation.Materials and methods.A case-control study enrolling 71 patients was organized. Inclusion criteria: DBD liver transplantation. Exclusion criteria: living related liver transplantation, reduced graft transplantation, recipient’s age fewer than 18.Results.Within rs5030717 there were identifi ed three genotypes: AA (81.6%) and two genotypes with the minor G-allele: AG (12.6%) and GG (5.6%). Within rs913930 there identi- fi ed three genotypes: TT (59.1%) and two genotypes with the minor C-allele: C/T (29.5%) and CC (11.2%). The rs11536865 studying revealed no polymorphism (GG genotype). The early allograft liver dysfunction (EAD) developed in 19.7% of patients, the severe EAD in 11.2% of patients, septic complications in 14%, acute cellular rejection in 23.9% of cases. The C/T genotype of the TLR-4 gene in the SNP rs913930 sequence was closely associated with the EAD development (OR 4.8 to 1; p = 0.047; 95% CI 1–23.4). Рatients with the donor’s liver C/T genotype had a reliably higher proportion (%) of the HMGB1 positive hepatocytes in the donor’s bioptate, 21 (17–29%) vs the СС+TT genotypes, 16 (10–19%) (Mann–Whitney test, p = 0.01). The CD68 expression in the liver bioptate at the donor’s stage was reliably higher in the carriers of heterozygotes in the SNP rs913930 (C/T genotype) and in the SNP rs5030717 (AG genotype), (Mann–Whitney test, p = 0.03). Signifi cant positive correlation between the CD68 expression in the donor’s liver bioptates and the IL-23 level in the hepatic vein has been determined in an hour after the portal reperfusion (ρ = 0.62; p = 0.04) as well as between the HMGB1 expression in the donor’s liver bioptates and the АSТ level in 24 hours after the reperfusion (r = 0.4; p = 0.02). The HMGB1 staining in the donor’s liver bioptates was higher in the EAD patients, 21 (20; 29) cells/mm2 in comparison with the patients without EAD, 16 (12; 18) (Mann–Whitney test, p = 0.0036).Conclusion.The early allograft liver dysfunction is associated with the genetic predisposition caused by the TLR-4 gene polymorphism and is implemented via the HMGB1, Kupffer cells and IL-23 activation.

Single Nucleotide Polymorphisms in IL8 and TLR4 Genes as Candidates for Digital Dermatitis Resistance/Susceptibility in Holstein Cattle

ABSTRACTRelatedness between single nucleotide polymorphisms in IL8 and TLR4 genes and digital dermatitis resistance/susceptibility was investigated in seventy Holstein dairy cows. Animals were assigned into two groups, affected group (n = 35) and resistant group (n = 35) based on clinical signs and previous history of farm clinical records. Blood samples were collected for DNA extraction to ampliy fragments of 267-bp and 382-bp for IL8 and TLR4 genes, respectively. PCR-DNA sequencing revealed three SNPs in each of IL8 and TLR4 genes. The identified SNPs associated with digital dermatitis resistance were C94T, A220G, and T262A for IL8 and C118T for TLR4. However, the G349C and C355A SNPs in TLR4 gene were associated with digital dermatitis susceptibility. Chi-square analysis for comparison the distribution of all identified SNPs in both IL8 and TLR4 genes between resistant and affected animals showed no significant variation among the identified SNPs in IL8 gene. Meanwhile, there was a significant variation in case of TLR4 gene. As a pilot study, the present results revealed that identified SNPs in IL8 and TLR4 genes can be used as a genetic marker and predisposing factor for resistance/susceptibility to digital dermatitis in dairy cows. However, TLR4 gene may be a potential candidate for such disease.

Analysis of TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms and mRNA level in patients with dengue infection: A case-control study

BackgroundDengue is a systemic viral infection that spreads to humans by the bite of infected Aedes mosquitoes. The secreted NS1 protein of dengue virus activates macrophages and human PBMCs via TLR4 and induce the release of pro-inflammatory cytokines which is responsible for the pathogenesis of disease. Mutations in TLR4 gene have been associated with the increased susceptibility to many viral, bacterial and parasitic diseases. ObjectiveTo study the impact of TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) gene polymorphisms with susceptibility to dengue infection. MethodsA total of 120 dengue infected (57; DHF/DSS and 63; DF) and 200 healthy controls were included in the study. TLR4 Asp299Gly and Thr399Ile gene polymorphisms was studied by PCR-RFLP. Expression of TLR4 mRNA was evaluated by rRT-PCR. ResultsIndividuals with heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms had increased susceptibility to dengue infection (OR-1.70, 95% CI=1.01–2.86 P=0.042 and OR-2.17, 95% CI=1.10–4.28, P=0.024, respectively). The frequency of Gly and Ile alleles were higher in dengue patients as compared to controls (OR-1.67, 95% CI=1.05–2.64, P=0.029 and OR-2.20, 95% CI=1.19–4.07, P=0.011, respectively). IIe/Gly haplotype was associated with the risk of the disease when compared with controls (OR=3.15, 95% CI=1.09–9.09, P=0.035). The mRNA expression was higher in DF when compared with DHF/DSS and controls (P=0.040 and 0.009, respectively). ConclusionA higher expression of TLR4 mRNA was associated with DF. The TLR4 Asp299Gly and Thr399Ile gene polymorphisms were associated with the susceptibility of dengue infection probably by altering the immune response.

English

Toll-like receptors (TLRs) are known to play important roles in human innate immune systems. Polymorphisms in and functions of TLRs have been investigated to identify associations with specific infectious diseases including tuberculosis (TB). This study was performed for 166 samples of unrelated individual&#39;s diagnosis of pulmonary tuberculosis and 98 household healthy samples. Genomic DNA was extracted from EDTA-anticoagulated peripheral blood. The alleles of (rs352140) TLR9 gene polymorphisms were detected using polymerase chain reaction restriction fragment length polymorphism. The resulting fragments were separated in 3% agarose gel electrophoresis. The sequence results generated by the forward and reverse sequencing primers were analyzed with the software program sequencing analysis. Sequence comparisons of three genotypes AG, AA, and GG were performed using the multiple-alignment algorithm in Megalign. The direct counting was used to determine the allele and genotype frequencies of each polymorphism. Hardy-Weinberg equilibrium (HWE) tests were performed in controls by Fisher exact test. Significant deviations from the Hardy-Weinberg equilibrium in the distribution of the TLRs SNP genotypes in TB patients and controls were not detected for the SNP TLR9rs352140 for both patients and controls. These results do not indicate a major influence of these putative functional TLR SNP on the susceptibility to (or protection from) tuberculosis in Egyptian population. &nbsp; Key words: Association, TLR9, tuberculosis, Egyptian population.

Role of TLR4 gene polymorphisms in the colorectal cancer risk modulation in ethnic Kashmiri population – A case–control study

BackgroundColorectal carcinogenesis has been found to be associated with the polymorphic status of Toll-like receptor 4 gene in various populations of the world. AimThe aim of the study was to determine the genetic association of TLR4 gene polymorphisms (Asp299Gly and Thr399Ile) with disease susceptibility and risk development in colorectal cancer (CRC) patients of Kashmir, India. Materials and methodsGenotype frequencies of TLR4 polymorphisms (Asp299Gly and Thr399Ile) were compared between 120 CRC patients and 200 healthy controls using PCR-RFLP method. ResultsWe did not find any significant association between the TLR4 gene polymorphisms and the CRC cases (p>0.05). However CT genotype (Thr399Ile) showed modest elevated risk of the development of CRC [OR=1.78 95% CI (0.88–3.5)]. Also G allele (AG genotype) of TLR-4 Asp299Gly polymorphism was found to be significantly associated with the male gender (p value=0.006) and involvement of Nodes (p value=0.01) whereas, T allele (CT genotype) of Thr399Ile polymorphism showed significant association with the smoking status (p value=0.03). ConclusionOur results suggest that TLR4 gene polymorphism is not a key modulator of the risk of developing colorectal cancer in Kashmiri population.

Single nucleotide polymorphisms in toll-like receptor genes and case-control association studies with bovine tuberculosis

Aim:Toll-like receptor 2 (TLR2) and TLR4 genes play critical roles in host recognition of Mycobacterium bovis infection and initiation of innate and adaptive immune response. The present study was aimed at exploring the association of seven single nucleotide polymorphisms (SNPs) in TLR2 and TLR4 genes with susceptibility/resistance against bovine tuberculosis (bTB) infection in cattle.Materials and Methods:A case-control resource population of 35 positive and 45 negative animals was developed after screening with single intradermal tuberculin test for bTB. Resource population was screened for SNPs in TLR2 and TLR4 genes using polymerase chain reaction-restriction fragment length polymorphism. The PROC LOGISTIC procedure of SAS 9.3 was used to find an association of allelic and genotypic frequencies with bTB.Results:In TLR2 gene, two of SNPs under study (rs55617172 and rs68268253) revealed polymorphism while in the case of TLR4 gene all four SNPs under investigation (rs8193041, rs207836014, rs8193060, and rs8193069) were found to be polymorphic in case-control population. SNP locus rs55617172 in TLR2 gene was found significantly (p<0.01) associated with susceptibility/resistance to TB in cattle.Conclusion:These findings indicate the presence of SNPs in TLR2 and TLR4 genes in our resource population. Upon validation in independent, large resource population and following biological characterization, SNP rs55617172 can be incorporated in marker panel for selection of animals with greater resistance to bTB.

25-Hydroxy Vitamin D, Vitamin D Receptor and Toll-like Receptor 2 Polymorphisms in Spinal Tuberculosis: A Case-Control Study.

Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such asTLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated serum vitamin D, and VDR and TLR-2 gene polymorphisms in patients with spinal tuberculosis.This study comprised of 3 groups: spinal tuberculosis, pulmonary tuberculosis, and controls (each with 106 subjects). Enzyme-linked immunosorbent assay was used to measure vitamin D levels, and polymerase chain reaction-sequencing method was used to analyze VDR and TLR-2 gene polymorphisms. Patients were followed up for 6 months.Vitamin D deficiency was significantly more prevalent in patients with spinal tuberculosis (P < 0.001) and pulmonary tuberculosis (P = 0.011), versus controls. The heterozygous and mutant genotypes of VDR TaqI gene were significantly associated with spinal tuberculosis (P < 0.001; odds ratio [OR] 4.74 [2.45–9.18]) and pulmonary tuberculosis (P < 0.001; OR 3.52 [1.80–6.88]) when compared with controls. The heterozygous and mutant variants of VDR ApaI gene were significantly more common in patients with spinal tuberculosis in comparison with patients with pulmonary tuberculosis (P < 0.001; OR 2.90 [1.65–5.10]) and controls (P < 0.001; OR 6.56 [3.41–12.61]). We did not observe any significantly different results for TLR-2 gene polymorphisms. Vitamin D deficiency, VDR, and TLR-2 polymorphisms did not affect the 6-month disability.Vitamin D deficiency and VDR gene polymorphisms are significantly more prevalent in people with pulmonary and spinal tuberculosis. They may, in isolation or collectively, confer susceptibility to pulmonary and spinal tuberculosis.

The TLR2 and TLR4 gene polymorphisms in Moroccan visceral leishmaniasis patients

Visceral leishmaniasis (VL) is endemic in the Mediterranean basin and leads to the most severe form of Leishmania infection, lethal if left untreated. However, most infections are sub-clinical or asymptomatic, reflecting the influence of host genetic background on disease outcome. This study aimed to investigate possible association of TLR4 Asp299Gly, TLR4 Thr399Ile and TLR2 Arg753Gln polymorphisms with VL in Moroccan children. We enrolled 119 children with VL caused by Leishmania infantum as well as 138 unrelated children, 95 asymptomatic subjects and 43 healthy individuals who had no evidence of present or past infection. Polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system assay (ARMS-PCR). Results showed significant differences in genotype Thr399Ile and recessive model frequencies between VL and delayed-type hypersensitivity (DTH+) groups (p=0.018, OR=0.414CI 0.195–0.880; p=0.029, OR=0.448CI 0.214–0.938], respectively) by having the amino-acid threonine polymorphism as a reference in the VL group. Concerning the Asp299Gly there were a significant associations when comparing VL vs DTH+ (Asp299Gly genotype p=0.002, OR=0.326CI 0.158–0.671, allele frequencies p=0.033, OR=0.396CI 0.164–0.959, recessive model p=0.002, OR=0.343CI 0.172–0.681) and DTH+ vs DTH- groups (Asp299Gly genotype p=2.160E-4, OR=3.065CI 1.672–5.618, Gly299Gly genotype p=0.047, OR=0.368CI 0.299–0.452, allele frequencies p=1.406E-7, OR=29.571CI 3.907–223.8, recessive model p=4.370E-14, OR=36.965CI 8.629–158.3), by having the aspartic acid polymorphism as a reference these results suggest that the allele A (savage) confer protection against the clinical manifestations but not against the infection. Furthermore, there was a significant association regarding the Arg753Gln genotype (p=0.002, OR=0.326CI 0.158–0.671), allele frequencies (p=0.033, OR=0.396CI 0.164–0.959) and when applying a recessive model (p=0.002, OR=0.343CI 0.172–0.681) in the VL vs DTH+ groups. The same results was observed when comparing DTH+ vs DTH- groups (p=4.136E-6, OR=0.211CI 0.104–0.428), allele frequencies (p=0.008, OR=0.327CI 0.137–0.779) and recessive model (p=1.748E-5, OR=0.244CI 0.124–0.480). The results provide evidence that allele C in Thr399Ile and allele G in Arg753Gln polymorphisms may lead to protection against the clinical disease. Our data provide insights into the possible role of TLR2 and TLR4 variations in VL susceptibility.

TLR4 Gene Polymorphism and its Association with Mastitis Resistance in Indigenous and Crossbred Cattle of Tamil Nadu, India

TLR4 gene is one of the candidate genes for mastitis resistance in cattle. This gene has three exons and PCR with nine sets of primers produced nine amplicons. The amplicons were sequenced from both ends, assembled and screened for SNPs. Totally, 221 dairy cows (Jersey crossbreds, Holstein Friesian crossbreds and indigenous breeds) were genotyped either by PCR-RFLP or tetra-primer ARMS-PCR. Genotyping results showed that one SNP was in 5’UTR region, two SNPs in intron 1, one in exon 2 and seven in exon 3. Out of 11 SNPs, allele frequencies were found to differ between healthy and mastitic cows in six SNPs viz. SNPs 245, 5053, 5134, 9422, 9787 and 9794. At SNP position 5134, the G allele frequency got reduced from 0.71 in healthy cows to 0.50 in mastitic cows but the A allele frequency increased from 0.29 in healthy cows to 0.50 in mastitic cows. The SNP 5053T>G resulted from transversion while the SNPs 5087G>A and 5134G>A resulted from transitions. In SNP 5134G>A, the frequency of both the alleles were in equal proportions in mastitic animals. The SNP 9787C>T in exon 3 had shown no appreciable change in the allele frequencies in both normal and mastitis animals. Homology modeling of TLR4 gene revealed no change in the length of the amino acids of TLR4 protein. The amino acid tyrosine present in the position 674 in the protein chain of Bos tauruswas replaced lysine in crossbreds. No association was found between TRL4 genotypes and somatic cell scores in the breeds studied.

Association between Toll-Like Receptor 4 and Occurrence of Type 2 Diabetes Mellitus Susceptible to Pulmonary Tuberculosis in Northeast China.

The purpose of this study is to explore why type 2 diabetes mellitus (T2DM) patients are susceptible to pulmonary tuberculosis through detection of serum Toll-like receptor 4 (TLR4), an important immune-related receptor, especially in terms of content and TLR4 gene polymorphism. Patients with T2DM complicated by pulmonary tuberculosis (T2DMTB) were selected as the case group and T2DM patients without tuberculosis were selected as the control group. Forty patients in each group were randomly selected and their serum TLR4 levels were detected and compared. Determination of six sites of TLR4 gene polymorphism was carried out in 238 T2DMTB patients and 310 patients with T2DM, and results showed that the serum TLR4 content of the T2DMTB group was significantly lower than that of the T2DM group (p < 0.05). The six sites of TLR4 gene polymorphism did not show significant associations with T2DMTB risk. No statistically significant differences in genotype distributions were observed between T2DMTB patients and patients with T2DM when studied using the recessive and dominant genetic models. How two diseases with contradictory nutritional statuses can occur in the same person is difficult to explain from environmental factors perspective alone. Future research should study the causes of T2DMTB from the perspective of genetics.

Prevalence of TLR-4 gene polymorphism in patients co-infected with HIV/HCV

There was studied the prevalence of Asp299Gly polymorphism of TLR-4 gene in patients co-infected with HIV-HCV.Methods. To define the frequency of Asp299Gly polymorphism of TLR-4 gene there were examined 47 patients co-infected with HIV\HCV and 30 healthy donors by the method of polymorphism of the long restrictive fragments (PLRF) – polymerase chain reaction (PCR). Among examined persons there were 21 (44,7 %) women, 26 (55,3 %) – men. The mean age was 36,2±2,4 years, from 21 to52 years old.Results. The correlative analysis indicates the reverse dependency between Asp299Gly polymorphism of TLR-4 gene and Zn content (r=-0,34; p&lt;0,05), relative numder of CD4+,% (r=-0,32; p&lt;0,05) in blood serum of patients co-infected with HIV\HCV. At the same time in patients co-infected with HIV\HCV there was noticed the direct dependency between Asp299Gly polymorphism of TLR-4 gene and α tumor necrosis factor (r=0,32; p&lt;0,05), С-reactive protein (r=0,34; p&lt;0,05), absolute number of СD3+ Т-lymphocytes (r=0,34; p&lt;0,05), TG level (r=0,39; p&lt;0,02), absolute numder of CD45+ Т-lymphocyte (r=0,45; p&lt;0,001), insulin level (r=0,66; p&lt;0,001) and insulin-resistance (r=0,66; p&lt;0,001).Conclusions: In patients co-infected with HIV\HCV the Asp299Gly polymorphism of TLR-4 gene is reliably more often than the control group (χ2=4,5; р&lt;0,05). The correlative analysis demonstrated the powerful direct dependency between Asp299Gly polymorphism of TLR-4 gene and clinical stage of disease in patients co-infected with HIV\HCV (r=0,43; p&lt;0,001)

TLR4 Gene Polymorphisms and Susceptibility to Gastric Carcinoma and Epstein-Barr Virus-associated Gastric Carcinoma in Northern China

TLR4 Gene Polymorphisms and Susceptibility to Gastric Carcinoma and Epstein-Barr Virus-associated Gastric Carcinoma in Northern China

Toll-like receptors TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) gene polymorphisms in end-stage renal disease patients on peritoneal dialysis.

Toll-like receptors (TLRs), expressed on cells of the innate immune system, are the first line of host defense. Recognition of bacterial pathogens by the peritoneum is mediated in part by TLR. In this study, we investigated the role of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) gene polymorphisms in end-stage renal disease (ESRD) patients on peritoneal dialysis (PD). A total of 100 ESRD patients on PD and 150 healthy controls were enrolled in the study. The patients were divided into two groups: ESRD patients on PD with peritonitis (n = 38) and without peritonitis (n = 62). Genotyping of TLR4 (Asp299Gly and Thr399Ile) and TLR2 (Arg677Trp and Arg753Gln) genes were performed by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). Heterozygous variant of TLR4 (Thr399Ile) Thr/Ile genotype showed significant association with both groups of patients (patients with and without peritonitis) with no difference between the groups. Overall, TLR4 (Thr399Ile) Thr/Ile genotype demonstrated an association with ESRD on PD (OR 3.9). Further, TLR4 (Thr399Ile) polymorphism showed significant association with PD patients having two or more episodes of peritonitis compared to patients with no peritonitis. No such association of increased risk of ESRD was observed with TLR4 (Asp299Gly) Asp/Gly genotype and TLR2 polymorphisms. Haplotype frequencies, Gly/Ile and Asp/Ile, conferred 2.46- and 4.62-fold increased risk of ESRD, respectively. TLR4 Thr399Ile genotype was associated with ESRD patients on PD; however, the genotype frequency was similar in PD patients with and without peritonitis.

Association of TLR4 gene polymorphisms with sporadic Parkinson's disease in a Han Chinese population.

Parkinson's disease (PD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, while previous studies point to a pivotal role of neuroinflammation in the pathophysiology of PD. As a member of pattern recognition receptors, TLR4 plays an important role in the immune response and inflammatory responses. Growing evidences suggest that mutation of TLR4 gene may be connected with the development of PD. The objective of this study was to evaluate whether genetic polymorphisms of the TLR4 gene are associated with PD susceptibility. We genotyped three single-nucleotide polymorphisms of the TLR4 gene (rs1927911, rs1927914 and rs10116253) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in unrelated 380 PD patients and 380 healthy-matched controls. Our study revealed that rs1927914 C allele carriers and C allele were probably related to a decreased risk of PD (p = 0.032 and p = 0.028, respectively) as well as male PD (p = 0.034) and early-onset PD (EOPD) (p = 0.023). In addition, there were significant differences in genotype and allele distribution in male PD patients and its healthy-matched control subgroup (p = 0.035 and p = 0.012, respectively). For rs1927911 and rs10116253 polymorphisms, genotype or allele frequencies did not differ between groups. Our data suggest that the TLR4 gene might contribute to the risk of developing PD in Han Chinese and rs1927914 polymorphism may be a protective factor for sporadic PD, male PD and EOPD.

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Immune dysfunction is thought to be animportant pathway underlying the association of childhood traumatic events withearly-onset of bipolar disorder (BD). The study of gene-environmentinteractions are important to better understand the genetics of resilience orsusceptibility to this severe subform of BD. We thus explored the potentialinteraction of genetic variants of TLR2 and TLR4 , major triggers of inflammatoryresponses in presence of pathogens, and the presence of childhood trauma on theage at onset of BD. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were analyzed in relation to age at onset of BD in531 BD patients genotyped for TLR2 rs 4696480and rs 3804099 and TLR4 rs 1927914 and rs 11536891, 329 of which completed the Childhood TraumaQuestionnaire. We report a combined effect of TLR2 rs 3804099TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve ( p = 0.02). Regression analysis was non-significant for the TLR2 -CTQ sexual abuse interaction term. The pathological effect of childhood adversity may be of greater importance in patients with an immuno-genetic susceptibility background. Further exploration of clinical characteristics of severity and immune phenotypes in BD may allow the development of innovative therapeutic interventions.

Genotyping of IL-10, TNFα and TLR4 gene polymorphisms in individuals with asymptomatic and chronic cutaneous leishmaniasis caused by Leishmania (Viannia)

Genotyping of IL-10, TNFα and TLR4 gene polymorphisms in individuals with asymptomatic and chronic cutaneous leishmaniasis caused by Leishmania (Viannia)

Association of TLR4 gene polymorphism with mastitis resistance and susceptibility in Frieswal cattle

Toll-like receptors (TLRs) are essential in the host defense against microbial pathogens. Individual TLRs recognize distinct structural components of pathogens and evoke inflammatory responses. In the present study, the amplicon of 316 bp of TLR4 gene was amplified in the thermal cycler (Gene Amp 6700, Applied Biosystem) using the primers of TLR4 gene and the genetic polymorphism was detected by Single Strand Conformation Ploymorphism (SSCP). The SSCP analysis of 316 bp region of TLR4 gene revealed similar type of SSCP patterns in healthy, subclinical and clinical mastitis cases suggesting that Frieswal cattle is monomorphic for TLR4 gene.