TLR4 Asp299Gly Research Articles

TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis.

Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding region of the toll-like receptor 4 gene (TLR4) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis (a major periodontal pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated with lipopolysaccharide-mediated inflammatory responses in periodontitis), have been largely ignored in previous reports. Therefore, the objective of this study was to examine the association between TLR4 Asp299Gly (rs4986790) with alveolar bone height loss (ABHL) and periodontitis, accounting for interactions between this SNP with smoking and P.gingivalis prevalence. The CD14/-260 SNP (rs2569190) served as a control, as a recent meta-analysis suggested no relationship between this SNP and periodontitis. This multicenter study included 617 participants who had rheumatoid arthritis or osteoarthritis. This report presents a secondary outcome from the primary case-control study examining the relationship of periodontitis with established rheumatoid arthritis. The Centers for Disease Control/American Academy of Periodontology case definitions of periodontitis were used for this analysis. Participants received a full-mouth clinical periodontal examination and panoramic radiograph. Percentage ABHL was measured on posterior teeth. The TLR4 Asp299Gly and CD14/-260 SNPs were selected a priori and genotypes were determined using the ImmunoChip array (Illumina(®) ). Minor allele frequencies and associations with periodontitis and ABHL did not differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, data from these two groups were pooled. The presence of P.gingivalis was detected in subgingival plaque by PCR. Multivariate ordinal logistic regression examined associations between the SNPs and periodontitis or ABHL. SNP interactions with smoking and P.gingivalis were analyzed. A significant, negative interaction was observed between the TLR4 SNP and the presence of P.gingivalis (p=0.045) with respect to periodontitis. The TLR4 minor variant was also associated with less ABHL: 16.8% of individuals with low ABHL, 9.0% with moderate ABHL and 11.2% with high ABHL had the minor allele [p=0.029; odds ratio=0.58 (95% confidence interval: 0.36-0.95)]. The interaction between the TLR4 SNP and smoking was not significant with respect to periodontitis or ABHL. The CD14 SNP was not associated with periodontitis or ABHL. The TLR4 Asp299Gly SNP significantly interacted with P.gingivalis in conferring a decreased risk of periodontitis and may be protective against ABHL, a feature of periodontitis. Agents blocking TLR4 signaling, a strategy currently under investigation for the treatment of other inflammatory conditions, may warrant investigation in the context of periodontitis related to the presence of P.gingivalis.

Associations between TLR4 Asp299Gly variant and Alzheimer’s-related pathological biomarkers

Associations between TLR4 Asp299Gly variant and Alzheimer’s-related pathological biomarkers

Toll-like receptor (TLR4) Asp299Gly and Thr399Ile polymorphisms in relation to clinical falciparum malaria among Nigerian children: a multisite cross-sectional immunogenetic study in Lagos.

IntroductionThis study determined the association of TLR4 Asp299Gly and Thr399Ile with uncomplicated and severe malaria among Nigerian children of similar ethnic background in Lagos. The association of these SNPs with high parasite density, malnutrition, hyperpyrexia and anaemia was also investigated.MethodsGenomic DNA of the study participants was screened for the genotypes of TLR4 Asp299Gly and Thr399Ile by PCR-RFLP. Anthropometric measurement was performed on the Pf infected children stratified into asymptomatic malaria (control), uncomplicated and severe malaria (case). Parasites were detected by light microscopy and Hardy Weinberg Equilibrium (HWE) of SNP genotypes was also determined.ResultsA total of 279 children comprising 182 children (62.1 % male; mean ± SEM age, 57.3 ± 1.7 months) with clinical falciparum malaria and 97 children (55.7 % male; mean ± SEM age, 55.6 ± 2.5 years) with asymptomatic falciparum malaria were enrolled. All the genotypes of both TLR4 SNPs were found in the study population with their minor alleles: 299Gly and 399Ile, found to be 17.6 % and 14.7 % in severe malaria children. Unlike in asymptomatic population, the genotype distribution of TLR4 Asp299Gly SNP was not in HWE in the clinical malaria group but did not condition susceptibility. However, Asp299Gly and Thr399Ile polymorphisms were found to increase the risk of severe malaria 3-fold and 8-fold respectively (P < 0.05). They also increased the risk of severe anaemia, high parasite density and severe malnutrition 3.8 -5.3-fold, 3.3 – 4.4-fold and 4-fold respectively.ConclusionsBased on the above findings, we conclude that TLR4 Asp299Gly and Thr399Ile polymorphisms may modulate susceptibility to severe malaria among Nigerian children of Yoruba ethnic background.

Immunity to endotoxin and Asp299Gly polymorphism of TLR-4 in adult patients with early and late onset of asthma

Aim. The gene polymorphism of Asp299Gly TLR-4 may be associated with the risk of asthma development.Methods and results. The gene polymorphism of TLR-4 (Asp299Gly) receptor has been researched in 262 early-onset and in 69 late-onset asthma patients. The state of anti-endotoxin immunity was assessed by determination of specific antibodies to the endotoxin of A, M, G classes and sCD14 by ELISA. The polymorphism was analyzed by the allele-specific polymerase chain reaction with electrophoretic detection. It was estimated that the risk of early-onset asthma in the population of Crimea is associated with genotypes AG and GG (Asp299Gly) of TLR-4. There were increased levels of anti-endotoxin IgM and decreased of sIgA in patients with late-onset asthma and AA genotype as compared to other genotypes.Conclusion. The gene polymorphism of Asp299Gly TLR-4 is associated with the risk of early-onset asthma development in Crimea population.

Toll like receptor-4 gene polymorphisms in patients with solitary cysticercus granuloma

BackgroundSolitary cysticercus granuloma (SCG) of the brain is the most common type of neurocysticercosis in India. In this study, we evaluated TLR4 polymorphisms in patients with SCG. MethodsOne-hundred-forty-three patients with SCG and 134 controls were enrolled. Assessment for TLR4 Asp299Gly and Thr399Ile polymorphism was done. TLR4 genotype was determined by PCR-sequencing chain termination method. The patients were followed for 6months. ResultsAsp/Gly (P=0.024) and Thr/Ile (P=0.004) genotypes were significantly associated with the SCG. The Gly (Asp/Gly plus Gly/Gly) genotype (P=0.025) and Ile (Thr/Ile plus Ile/Ile) genotype (P=0.008) were significantly associated with the SCG. Gly/Gly and Ile/Ile genotypes were not significantly associated with SCG (P=0.767 for Gly/Gly, P=0.936 for Ile/Ile). At 6months, TLR4 299Asp/Gly (P=0.02) and 399Ile/Thr (P=0.023) polymorphisms were significantly associated with the calcification or persistence of SCG. ConclusionsTLR4 polymorphisms are associated with the susceptibility to infection with SCG.

Early-Onset Asthma Is Associated with a Specific Polymorphisms of TLR-4 (Asp299Gly) in Ukrainian Adults

Early-Onset Asthma Is Associated with a Specific Polymorphisms of TLR-4 (Asp299Gly) in Ukrainian Adults

Evaluation of TLR2 and TLR4 Polymorphisms in Chronic HBV Infection

Aims: Toll - like receptors ( TLR s) play a central role in initiating innate response by mediating inflammatory reactions against a wide range of pathogens. We aimed to determine if TLR2 Arg753Gln, TLR4 Asp299Gly and Thr399Ile polymorphisms are associated with chronic hepatitis B (HBV) infection. Study Design: A case - control study . Methodology: Genomic DNA was obtained from peripheral blood of 100 patients with chronic HBV infection and 108 healthy volunteer controls. The TLR2 and TLR4 polymorphisms were Original Research Article

The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals.

BackgroundHIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals.MethodsPatients with no pre-existing CVD risk factors on suppressive antiretroviral therapy were recruited from University Malaya Medical Centre, Malaysia (n = 84). The CD14 C-260T and TLR4 SNPs, Asp299Gly and Thr399Ile were genotyped and soluble(s) CD14 and sCD163 and high-sensitivity C-reactive protein, hsCRP were measured in plasma. Subclinical atherosclerosis was assessed by measuring carotid intima media thickness (cIMT). The association between CD14 C-260T SNP carriage and cIMT was assessed in a multivariable quantile regression model where a p-value of <0.05 was considered significant.ResultsWe found the CD14 C-260T T-allele in 56% of the cohort and evidence of subclinical atherosclerosis in 27%. TT genotype was associated with higher sCD163 (p = 0.009) but only marginally higher sCD14 (p = 0.209) and no difference in hsCRP (p = 0.296) compared to CC/CT. In multivariable analysis, only Framingham risk score was independently associated with higher cIMT while lower sCD163 was trending towards significance. No association was found in TT-genotype carriers and cIMT measurements.ConclusionThe CD14 C-260T SNP was associated with increased monocyte activation but not systemic inflammation or cIMT in this HIV-infected cohort with low CVD risk profile.

Polymorphisms of Toll-Like Receptor 4 as a Risk Factor for Periodontitis: Meta-Analysis.

Toll-like receptors play an important role in the recognition of periopathogens. There are widely known polymorphisms of these receptors that may alter host susceptibility to periodontitis. Evaluating the association of TLR4 polymorphisms (Asp299 and Thr399Ile) with the occurrence of periodontitis and its two clinical types: chronic (CP) and aggressive (AgP) among Caucasians. A review of 4 electronic databases was made to identify studies that match the inclusion criteria for the meta-analysis and were published up to December 31, 2013. Fifteen studies met the inclusion criteria. For Asp299Gly polymorphism 1621 patients with periodontitis (1148 with CP and 473 with AgP) and 1755 individuals without clinical signs of periodontitis were included in the meta-analysis. The occurrence of polymorphism The 399Ile was evaluated among 1522 patients with periodontitis (1017 with CP and 505 with AgP) and 1461 subjects in the control group. The pooled OR with a random effects model for the Asp299Gly and chronic periodontitis was 1.35 (95% CI: 1.02-1.8, p = 0.038), indicating a possible association between this polymorphism and CP. Other published meta-analyzes showed no significant association between single nucleotide polymorphisms of TLR4 and periodontitis nor its clinical types. No publication bias was reported. Our meta-analysis showed statistically significant association between TLR4 Asp299Gly allele and increased susceptibility to chronic periodontitis.

Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia

Infectious complications continue to be one of the major causes of morbidity and mortality in patients with acute myeloid leukemia (AML). Several single-nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) can affect the genetic susceptibility to infections or even sepsis. We sought to investigate the impact of different SNPs on the incidence of developing sepsis and pneumonia in patients with newly diagnosed AML following induction chemotherapy. We analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) gene in a cohort of 155 patients with AML who received induction chemotherapy. The risk of developing sepsis and pneumonia was assessed by multiple logistic regression analyses. The presence of the TLR2 Arg753Gln polymorphism was significantly associated with pneumonia in AML patients (odds ratio (OR): 10.78; 95% confidence interval (CI): 2.0-58.23; P=0.006). Furthermore, the cosegregating TLR4 polymorphisms Asp299Gly and Thr399Ile were independent risk factors for the development of both sepsis and pneumonia (OR: 3.55; 95% CI: 1.21-10.4, P=0.021 and OR: 3.57, 95% CI: 1.3-9.86, P=0.014, respectively). To our best knowledge, this study represents the first analysis demonstrating that polymorphisms of TLR2 and TLR4 influence the risk of infectious complications in patients with AML undergoing induction chemotherapy.

Association of Toll like receptor Asp299Gly with rheumatoid arthritis risk: A systematic review of case–control studies and meta-analysis

ObjectiveRheumatoid arthritis (RA) is thought to be triggered by various genetic and environmental factors. Few human epidemiologic studies demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are associated with RA. We aimed to evaluate the effects of TLR polymorphisms on the risk of RA pathogenesis by using a meta-analysis approach. MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature was conducted. We screened the medical literature based on keywords search in MEDLINE and EMBASE ‘Toll-like receptor’, ‘polymorphism’, and rheumatoid arthritis. Meta-analyses were performed under the random-effects model by using: (1) recessive, (2) homozygous, (3) dominant, (4) codominant and allele contrast models. ResultsA total of 3086 cases and 3756 controls in nine studies were included in the meta-analysis. Association between TLR4 Asp299Gly and RA risk was marginally significant [OR=0.856 (95% CI, 0.716–1.022); P=0.086] in the homozygous model. AA and GG homozygote genotypes tended to be significant protective factors against RA risk. ConclusionOur overall analyses indicated that TLR4 Asp299Gly polymorphism might contribute to RA pathogenesis.

Association of Single Nucleotide Polymorphisms in Toll-like Receptor Genes With Asthma Risk: A Systematic Review and Meta-analysis.

PurposeAsthma is a complex disease, with contributions from multiple genes, various genetic backgrounds, and environmental factors. Many human epidemiological studies have demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are inconsistently associated with asthma risk. Some have demonstrated differences concerning the study design and effect size, and conflicting results have been reported. A meta-analysis is necessary to determine the magnitude of this association.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic search and meta-analysis of the literature was conducted to estimate the association of SNPs in TLR genes with asthma risk. We screened the medical literature based on the following keyword searches in MEDLINE and EMBASE databases: 'TLR', 'polymorphism', 'asthma', and their combinations.ResultsMeta-analysis of eight studies on TLR4 Asp299Gly showed a marginal association of TLR4 with asthma risk (odds ratio [OR]=0.814 [95% confidence interval [CI], 0.652-1.016; P=0.069]) in the recessive model. TLR4 Thr399Ile was not associated with asthma risk under any genetic model. Meta-analysis of four studies on TLR2 Arg753Gln indicated that TLR2 might be significantly associated with asthma in the dominant and codominant models (P=0.029, P=0.030, and P=0.009, respectively). TLR9 -1237 was marginally associated with asthma risk (OR=0.408 [95% CI, 0.163-1.021; P=0.065]) in the codominant model. Analysis using the allele contrast model showed that the major TLR9 -1237 T allele tended to be a significant protective factor with OR=0.689 (95% CI, 0.471-1.007; P=0.055).ConclusionsThe results showed that TLR4 Asp299Gly, TLR2 Arg753Gln, and TLR9-1237 might contribute significantly to asthma susceptibility. Future genetic association studies would consolidate these findings.

Involvement of Toll-like receptors in cervical cancer susceptibility among Tunisian women

Previous studies underscored the importance of genetic factors in the pathogenesis of certain cancers, including cervical cancer. Epidemiological evidence supports an association between specific polymorphisms of Toll-like receptors (TLR) with several human pathological states, including cervical cancer. The aim of this study was to investigate the link between specific gene variants in TLR2 (-196 to -174 del), TLR3 (c.1377 C>T), TLR4 (Asp299Gly), and TLR9 (2848 G>A) and susceptibility to cervical cancer in Tunisian women. Study subjects comprised 122 women with histopathologically-confirmed cervical cancer, and 260 unrelated age- and ethnically-matched healthy females, who served as controls. TLR genotyping was done using PCR-restriction fragment length polymorphism. The C/C genotype of TLR3 (c.1377 C>T) is associated with cervical cancer susceptibility (OR: 1.71, CI: 1.08-2.70). For TLR4 (Asp299Gly), the Asp/Asp genotype and the Asp allele were associated with higher risk of developing cervical cancer (OR: 4.95, CI: 1.97-13.22) and (OR: 5.17, CI: 2.11-13.50) respectively. We demonstrated no association between the TLR2 (-196 to -174 del) and the TLR 9 (2848 G>A) polymorphisms and the susceptibility of cervical cancer among Tunisian women. However, the C/C genotype for the TLR3 (c.1377 C>T) polymorphism and the Asp/Asp genotype and the Asp allele for (Asp299Gly) TLR4 polymorphism were found to be associated with a higher risk of cervical cancer.

O-224 Toll-like Receptors Genotype Polymorphism In Egyptian Children With Chronic Viral Hepatitis C

Background Toll-like receptors (TLRs) are important molecules for both innate and adaptive immune responses. The prevalence of TLRs polymorphism varies in different populations and controversial results were reported in HCV patients. We aimed to assess the frequency of TLR2 Arg753Gln, TLR4 Asp294Gly and TLR4 Thr399Ile polymorphisms among Egyptian children with chronic HCV and to study their relation to clinical data. Methods An observational case control study was conducted in Mansoura University Children’s Hospital, Egypt and included 100 Chronic HCV patients (63% males) with mean age of 13 ± 2.8 years in addition to 100 healthy matched controls. Diagnosis of patients relied upon persistently positive HCV PCR for at least 6 months. Eighty two patients received combined pegylated interferon α2b 60 mcg/m 2 /w and ribavirin 15 mg/kg/d. Treatment was continued for 48 weeks for responders (49 patients). All subjects were exposed to history, examination, liver functions, viral markers, HCV PCR and abdominal ultrasound. Liver biopsy was done only for patients. Gene polymorphisms were assessed by restriction fragment length polymorphism. Results Neither patients nor controls had TLR2 Arg753Gln or TLR4 Asp299Gly polymorphisms. Only 3 patients (3%) were heterozygous for TLR4 Thr399Ile polymorphism without significant difference between patients and controls (p = 0.24). No significant correlation was observed between TLR4 Thr399Ile polymorphism and viral load, histologic activity, grade of fibrosis or treatment response (p = 0.96, 0.21, 0.46, 0.49 respectively). Conclusion TLR2 Arg753Gln, TLR4 Asp294Gly and TLR4 Thr399Ile polymorphisms seem to be absent or rare and probably have no role in HCV among Egyptian population.

Toll-like receptor 4 mediates endothelial cell activation through NF-κB but is not associated with endothelial dysfunction in patients with rheumatoid arthritis.

ObjectiveTo investigate the effects of TLR4 antagonism on human endothelial cells activation and cytokine expression, and whether the Asp299Gly TLR4 polymorphism is associated with better endothelial function in patients with rheumatoid arthritis (RA).MethodsHuman aortic endothelial cells (HAECs) were treated with lipopolysaccharide (LPS), OxPAPC, and free fatty acids (FFA) at baseline and after incubation with the TLR4 antagonist eritoran (E5564). Cytokine expression was assessed by quantitative real-time PCR. In vivo endothelial function was assessed as brachial artery flow-mediated dilation (FMD) in RA patients with the wild type gene (aa) and with the Asp299Gly TLR4 polymorphic variant (ag).ResultsIn HAEC, TLR4 antagonism with eritoran inhibited LPS-induced mRNA expression of IL-6, IL-8, TNFα, CCL-2, VCAM and ICAM (P<0.05 for all) and inhibited Ox-PAPC-induced mRNA expression of IL-8 (P<0.05) and IL-6, albeit not to a statistically significant level (p = 0.07). In contrast, eritoran did not affect FFA-induced mRNA expression of IL-6 (P>0.05). In 30 patients with RA (15 with the ag allele) undergoing measurement of FMD, no differences in FMD and plasma levels of IL-6, IL-8, VCAM, and ICAM were found between the aa and the ag phenotype (P>0.05 for all).ConclusionsTLR4 signaling in endothelial cells may be triggered by LPS and oxidized phospholipids, leading to endothelial activation and inflammation, which are inhibited by eritoran. Our in vivo investigation, however, does not support an association between the Asp299Gly TLR4 polymorphism and improved endothelium-dependent vasodilator function in patients with RA. Further study is needed to better understand the potential role of TLR4 on endothelial dysfunction in this and other patient populations.

Relationship between toll-like receptor 2 Arg677Trp and Arg753Gln and toll-like receptor 4 Asp299Gly polymorphisms and cytomegalovirus infection

The association among specific single-nucleotide polymorphisms (SNPs) in TLR2 (Arg677Trp, Arg753Gln) and TLR4 (Asp299Gln) and human cytomegalovirus (CMV) infection was studied in infants and adults. The TLR2 and TLR4 polymorphisms were genotyped in 151 patients with CMV infections and in 78 unrelated healthy individuals. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis of PCR-amplified fragments. The viral load was measured by quantitative real-time PCR. Almost all of the patients with CMV infections were wild-type homozygotes without TLR2 and TLR4 polymorphisms. No significant differences in TLR2 and TLR4 polymorphisms were observed between infants with or without CMV infection. Compared with adults with CMV infections, heterozygosity for the TLR2 Arg677Trp and TLR4 Asp299Gly SNPs was detected more frequently in healthy individuals (p<0.05). Logistic regression analysis showed that the wild-type TLR2 genotype was associated with an increased risk of CMV infection and that heterozygosity for TLR2 and TLR4 SNPs diminished the risk of CMV infection in adult patients. An association between CMV load and the TLR4 SNP was found. Our results suggest that the wild-type TLR2 genotype may be a risk factor for CMV replication in adult patients.

Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in ovarian cancers.

Toll-like receptor (TLR4) 4 is present in numerous cell types and serves as the first point of defense in the innate immune system. Single-nucleotide polymorphisms (SNPs) are present in a number TLR genes and have been associated with various infection and inflammation disorders. Asp299Gly and Thr399Ile, TLR4 SNPs, are associated with tumor progression. In the present study, cases of ovarian cancer were analyzed with regards to Asp299Gly and Thr399Ile of the TLR4 gene. Genotype analysis was performed using DNA from tissue samples from stage I–IV patients with ovarian cancer. DNA from tissue samples was extracted and analyzed by a pyrosequencing method following multiplex polymerase chain reaction. The genotypes of these SNPs were analyzed in the present study in a population of 105 patients, with different types of ovarian cancer, between 2004 and 2012. The allele frequencies for TLR4 Asp299Gly identified in this population were 1.00 (A) and 0.00 (G); for TLR4 Thr399Ile the allele frequencies were; 1.00 (C) and 0.00 (T). For TLR4 Asp299Gly the observed genotype frequency was 1.00 (AA), 0.00 (AG) and 0.0 (GG). In TLR4 Thr399Ile the observed genotype frequencies were 1.00 (CC), 0.00 (CT) and 0.00 (TT). TLR4 Asp299Gly and Thr399Ile alleles were not detected in the patients. These results indicated that the TLR4 299Gly and 399Ile alleles were exhibited at a lower frequency in the ovarian cancer patients that were examined.

Polymorphisms of toll-like receptors 2, 3 and 4 in patients that do and do not enter labour spontaneously at term

To assess the association of polymorphisms of toll-like receptors (TLRs) 2, 3 and 4 with the delay in onset of labour at term pregnancies, patients delivering at > 37 weeks and without pre-eclampsia, IUGR or a history of preterm delivery were prospectively evaluated. TLR2 Arg753Gln, TLR3 (c.1377C/T) and TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped by using PCR-RFLP. Patients labouring spontaneously before the 41st week were compared with those who did not labour spontaneously until this week in terms of baseline characteristics, TLR 2, 3 and 4 polymorphisms. The same comparisons were also performed by using a 40th week cut-off. Chi-square test, two-sample t-test or Mann–Whitney U tests were used for comparisons, as appropriate. In total, 79 patients delivering after 37 weeks were evaluated. All had CC genotype for TLR2 Arg753Gln and TLR4 Thr399Ile. There were no significant differences for TLR4 Asp299Gly GA and TLR3 (c.1377C/T) polymorphisms between patients spontaneously entering or not entering labour until the 41st week; the same was true when the 40th week cut-off was used. Delay in onset of labour at term pregnant women does not seem to be affected by the presence of TLR 2, 3 or 4 polymorphisms. Further studies are needed.

May TLR4 Asp299Gly and IL17 His161Arg polymorphism be associated with progression of primary measles infection to subacute sclerosing panencephalitis?

SSPE is a progressive neurological disorder of children. Only some of the children who are infected with measles virus develop SSPE, which supports individual variation. TLR-2 and TLR-4 play an important role in innate immunity by recognizing envelope proteins of MV. Another important cytokine that plays an important role in orchestrating innate immune function is IL-17. The purpose of our study is to elucidate whether the TLR2, TLR4, IL17F and IL17A gene polymorphisms are susceptibility genes for the development of SSPE. Using the PCR-RFLP methods, the single nucleotide polymorphisms of TLR2 (Arg753Gln, Arg677Trp, -194 to -174 del), TLR4 (Asp299Gly and Thr399Ile) IL17F (His161Arg, Glu126Gly) and IL17A were studied in 54 patients with SSPE and 81 healthy controls. For Asp299Gly polymorphism of the TLR4 gene we found that there were no control individuals who were homozygous carriers of the Gly/Gly genotype, and the risk for SSPE increased at approximately 4.7 fold for the heterozygous carriers of the Asp/Gly genotype (OR 4.727, 95%-CI 1.192-18.742; P=0.01), when compared to healthy controls. Also our findings demonstrate that homozygosity for the Arg161 variant of the IL17F His161Arg polymorphism is inversely associated with development of SSPE (OR 0.114 95%-CI 0.026-0.494; P<0.001). In conclusion, it is suggested that variation in susceptibility to SSPE disease may be in part due to variations in TLR4 and IL17 function resulting from polymorphisms of TLR4 Asp299Gly and IL17F His161Arg.

Genotypic analysis of Asp299Gly and Thr399Ile polymorphisms of TLR4 in Egyptian patients with rheumatoid arthritis and systemic lupus erythematosus

Toll-like receptors (TLRs) are essential molecules of the innate immune system that stimulate numerous inflammatory pathways and harmonize systemic defense against a wide array of pathogens. TLRs may also recognize a number of self-proteins and endogenous nucleic acids. Inappropriate stimulation of the TLR pathway by endogenous or exogenous ligands or as a consequence of mutation in the TLR genes may lead to induction and/or prolongation of autoimmune response and tissue injury. This study was designed to detect the TLR4 (Asp299Gly and Thr399Ile) gene polymorphism in Egyptian patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) as well as its correlation with disease activity. This study enrolled 50 patients who were attending the internal medicine and immunology out-patient clinic of Beni-Suef University Hospital. They were classified into three groups: 20 patients with RA, 20 patients with SLE, and 10 healthy controls. All studied persons were subjected to complete clinical evaluation, laboratory investigations, and detection of mutation in the TLR4 (Asp299Gly and Thr399Ile) gene by PCR technique. No individual in the RA patients group, the SLE patients group, or control population was identified carrying the Asp299Gly and Thr399Ile polymorphisms; in other words, all RA patients, SLE patients, and controls were with the same wild genotype. The similarity in genotype between the patients group and control population concluded that these two missense polymorphisms do not contribute to RA and SLE in a group of Egyptian population.