Asp299Gly Polymorphism Research Articles

Association between Toll-like receptor 4 Asp299Gly polymorphism and coronary heart disease susceptibility.

Published data on the association between Toll-like receptor 4 (TLR4) Asp299Gly polymorphism and coronary heart disease (CHD) susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. English-language studies were identified by searching PubMed and Embase databases (up to November 2016). All epidemiological studies were regarding Caucasians because no TLR4 Asp/Gly and Gly/Gly genotypes have been detected in Asians. A total of 20 case-control studies involving 14,416 cases and 10,764 controls were included in the meta-analysis. Overall, no significant associations were found between TLR4 Asp299Gly polymorphism and CHD susceptibility in the dominant model (OR=0.89; 95%CI=0.74 to 1.06; P=0.20) pooled in the meta-analysis. In the subgroup analysis by CHD, non-significant associations were found in cases compared to controls. When stratified by control source, no significantly decreased risk was found in the additive model or dominant model. The present meta-analysis suggests that the TLR4 Asp299Gly polymorphism was not associated with decreased CHD risk in Caucasians.

Role of Thr399Ile and Asp299Gly polymorphisms of toll-like receptor-4 gene in acute dental abscess.

BackgroundApical Periodontitis (AP) is an inflammatory disease that affects the tissues surrounding the root end of a tooth. The disease which is caused by endodontic infections presents in different clinical ways including development of an acute abscess. Recent studies have provided information suggesting role of a multitude of factors in pathogenesis of acute apical abscess (AAA). In this case-control study, our goal was to evaluate the frequency and potential role of two common polymorphisms of toll like receptor-4 (TLR-4) gene; Thr399Ile (1196 C>T) and Asp299Gly (+896 A>G), in 50 patients with AAA as cases and 50 patients with asymptomatic apical periodontitis (AAP) as controls.Material and MethodsSaliva sample containing mucosal epithelial cells was used for DNA extraction. Polymorphisms were detected by Tetra-ARMS (Amplification Refractory Mutation System) PCR method. Statistical analyses were carried out in SPSS 21 software.ResultsHomozygous wild type (CC) and heterozygous (CT) genotypes of Thr399Ile polymorphism were detected in 84% and 16% of AAA patients respectively. In controls, respective ratios were 94% (CC) and 6% (CT). Observed difference was not statistically significant (P>0.05) for distribution of these genotypes. The mutant homozygous (TT) genotype of this polymorphism was identified in neither of the participants. Overall, T allele frequency was obtained 8% in AAA and 3% in AAP (OR=2.6, 95% CI; 0. 6-10.6, p>0.05). For Asp299Gly polymorphism, no individual was detected with the mutant allele in case or control groups.ConclusionsOur results indicated a possible role for Thr399Ile polymorphism in acute presentations of abscess in AAA. However, the impact of this polymorphism needs to be more assessed in future studies. Key words:Genetic polymorphism, periapical abscess, periapical periodontitis, toll-like receptor 4.

Analyzing the correlation of TLR-4 Asp299Gly and Thr399Ile polymorphism in women with Bacterial Vaginosis in Hillah city.

Women in fecundity age have different vaginal infections , the commonly is bacterial vaginosis. Different microorganisms causes bacterial vaginosis, One of them were anaerobes that considered as vaginal flora and there presents in large number due to decrease in Lactobacilli growth lead to causing vaginal infections, where toll-like receptor-4 (TLR-4) can be stimulating by induces of immune response with these microbes. The association of TLR4polymorphism with the incidence of bacterial vaginosis among women was investigated in this study. High vaginal swabs and blood samples were obtained from 150 married women plagued from bacterial vaginosis and 150 unailing ladies as control. Human DNA was extracted, and TLR4 gene was amplified using specific primers. Restriction fragment length polymorphism technique was used for genotyping. Two single nucleotide polymorphisms (SNPs) (Asp299Gly and Thr399Ile) were investigated their relation with bacterial vaginosis. There is insignificant association between Thr399Ile and bacterial vaginosis (OR=0.765, 95%CI= 0.319-1.834 , p= 0.001). The SNPs of Thr399Ile canbe indicated to the susceptibility to get bacterial vaginosis.

Disseminated cysticercosis: clinical spectrum, Toll-like receptor-4 gene polymorphisms and role of albendazole: A prospective follow-up of 60 cases with a review of 56 published cases.

In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India.Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available.There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll-like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment.Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in 27 patients. Of the 4 deaths recorded, 3 had a heavy parasitic load and died after praziquantel therapy.Toll-like receptor-4 gene polymorphisms are associated with an increased susceptibility to disseminated cysticercosis, in the Indian population. Albendazole treatment seems to reduce the lesion load and improve symptoms.

Clinical characteristics and frequency of TLR4 polymorphisms in Brazilian patients with ankylosing spondylitis

ObjectivesInnate immunity is involved in the physiopathology of ankylosing spondylitis (AS), with the participation of Gram-negative bacteria, modulation of human leukocyte antigen (HLA) B27 and the involvement of pattern recognition receptors, such as Toll-like receptors (TLRs). The aim of this study was to investigate the clinical characteristics and frequency of TLR4 polymorphisms (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. MethodsA cross-sectional study was carried out involving 200 patients with a diagnosis of AS and a healthy control group of 200 individuals. Disease activity, severity and functional capacity were measured. The study of TLR4 polymorphisms was performed using the restriction fragment length polymorphism method. HLA-B27 was analyzed by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was used for the statistical analysis, with p-values less than 0.05 considered significant. ResultsMean age and disease duration were 43.1±12.7 and 16.6±9.2 years, respectively. The sample was predominantly male (71%) and non-Caucasian (52%). A total of 66% of the group of patients were positive for HLA-B27. The sample of patients was characterized by moderate functional impairment and a high degree of disease activity. No significant association was found between the two TLR4 polymorphisms and susceptibility to AS. ConclusionsTLR4 polymorphisms 399 and 299 were not more frequent in patients with AS in comparison to the health controls and none of the clinical variables were associated with these polymorphisms.

Polymorphisms of TLR4 Asp299Gly and TNF-α -308G/A in Leptospirosis

AbstractBackground : TLR4 Asp299Gly and TNF-α -308G/A polymorphisms have been shown to be associated with increased susceptibility and severity of infection. TLR4 Asp299Gly polymorphism could affect the host’s ability to respond to leptospira sp. TNF-α -308G/A polymorphism, is associated with the high producer of TNF-α.Methods : Total of 36 leptospirosis patients (IgM anti leptospira and MAT positive) and healthy individual with the equal number were included. The polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using site spesific restriction enzyme.Results : Distribution of homozygous wild-type TLR4 Asp299Gly polymorphism was higher in both of groups ( 94.5:97.2%.) and homozygous mutant allele was absent. There was not significantly difference of TLR4 Asp299Gly in leptospirosis patients and healthy group ( ρ=1.00; OR 0.5; 95%CI, 0.04-5.6) and between mild and severe leptospirosis (ρ=0.54; OR 1.54 ; 95% CI, 1.20-1.98). The presence of homozygous wild-type TNF-α -308G/A polymorphism was higher between leptospirosis patients and healthy group (100:94.5%) andhomozygous mutant allele was not found in both of the groups. No significantly different of TNF-α -308G>A polymorphism between leptospirosis patient and healthy group (ρ=0.49).Conclusions : In this study, the polymorphisms of TLR4 Asp299Gly and TNF-α -308G/A were not associated with the susceptibility and severity of leptospirosis. Keywords : Leptospirosis, TLR4 Asp299Gly polymorphism, TNF-α -308G/A polymorphism

Association of TLR-4 regulatory variants (rs41426344 and rs7873784) with rheumatoid arthritis in a Chinese population

Toll-like receptors (TLRs) play a key role in both innate and adaptive immunity. The role of TLR-4 in various autoimmune disorders has been well documented. Variations in the TLR-4 gene have been linked with susceptibility to rheumatoid arthritis (RA). In the present report, we conducted a hospital-based case-control study to investigate whether common polymorphisms in the TLR-4 gene are associated with susceptibility/resistance to development of RA in a Chinese population. A total of six single nucleotide polymorphisms (Asp299Gly, Thr399Ile, rs10759932, rs41426344, rs11536889, and rs7873784) were genotyped by PCR-RFLP in 250 RA patients and 248 healthy controls. Distribution of genotypes and alleles in RA and controls were compared by Fisher’s exact test. The prevalence of minor allele, heterozygous and homozygous mutants for rs41426344 polymorphism were more frequent in RA patients compared to healthy controls (C: P <0.0001, OR = 5.51 [3.37–8.99]; GC: P <0.0001, OR = 7.38 [4.10–13.29]; CC: P = 0.01, OR = 4.73 [1.28–17.47]). Similarly, the frequencies of CC genotype and C allele of rs7873784 polymorphism were significantly higher in RA than healthy controls ([GC: P = 0.008, OR = 1.77 [1.16–2.70]; C: P = 0.01, OR = 1.61 (1.11–2.34]). However, genotypes and alleles distribution of rs10759932 and rs11536889 were comparable in both clinical categories. Similar to earlier observations, all participants were wild type for TLR-4 codon polymorphisms (Asp299Gly and Thr399Ile). In conclusion, TLR-4 (rs41426344 and rs7873784) variants are associated with susceptibility to development of RA in a Chinese population.

Características clínicas e frequência de polimorfismos em TLR4 em pacientes brasileiros com espondilite anquilosante

ObjectivesInnate immunity is involved in the physiopathology of ankylosing spondylitis (AS), with the participation of Gram‐negative bacteria, modulation of human leukocyte antigen (HLA) B27 and the involvement of pattern recognition receptors, such as Toll‐like receptors (TLRs). The aim of this study was to investigate the clinical characteristics and frequency of TLR4 polymorphisms (Asp299Gly and Thr 399Ile) in a cohort of Brazilian patients with AS. MethodsA cross‐sectional study was carried out involving 200 patients with a diagnosis of AS and a healthy control group of 200 individuals. Disease activity, severity and functional capacity were measured. The study of TLR4 polymorphisms was performed using the restriction fragment length polymorphism method. HLA‐B27 was analyzed by conventional polymerase chain reaction. The IBM SPSS Statistics 20 program was used for the statistical analysis, with p‐values less than 0.05 considered significant. ResultsMean age and disease duration were 43.1±12.7 and 16.6±9.2 years, respectively. The sample was predominantly male (71%) and non‐Caucasian (52%). A total of 66% of the group of patients were positive for HLA‐B27. The sample of patients was characterized by moderate functional impairment and a high degree of disease activity. No significant association was found between the two TLR4 polymorphisms and susceptibility to AS. ConclusionsTLR4 polymorphisms 399 and 299 were not more frequent in patients with AS in comparison to the health controls and none of the clinical variables were associated with these polymorphisms.

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.

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.

The effect of Toll-like receptor 4 gene polymorphism on vascular complications in type 2 diabetes patients

ObjectiveThe aim of our study was to assess the association between the TLR4 Asp299Gly polymorphism and vascular complications in patients with type 2 diabetes. MethodsWe examined 1090 patients with T2DM and 716 healthy controls. All subjects were genotyped for the Asp299Gly polymorphism by polymerase chain reaction (PCR) and restriction analysis. ResultsThe genotype frequencies of the Asp299Gly polymorphism were similar in T2DM patients and controls (p=0.512 and 0.311, respectively). The polymorphism was analyzed in subgroups of patients with macro- and microvascular complications. The distribution of genotypes was significantly different between patients with CVD and those without CVD. A significant increase of G allele frequency was observed in CVD+ patients, with odds ratio 2.06 (1.27–3.34), p=0.0035. The same effect was found when patients with diabetic retinopathy were compared with those without it (OR for G allele 2.12, 95% CI 1.43–3.12, p=0.0002). There were no statistically significant differences in genotype distribution between patients with diabetic nephropathy or neuropathy and those without these complications. ConclusionsThe results of our study demonstrated that the G allele of the Asp299Gly polymorphism of the TLR4 gene is associated with increased risk of cardiovascular disease and diabetic retinopathy in type 2 diabetes patients.

Toll-like Receptor-4 Polymorphisms and Serum Matrix Metalloproteinase-9 in Newly Diagnosed Patients With Calcified Neurocysticercosis and Seizures.

We evaluated seizure profile, Toll-like receptor (TLR)-4 polymorphisms, and serum matrix metalloproteinases (MMPs) in patients with calcified neurocysticercosis.One-hundred nine patients with calcified neurocysticercosis with newly diagnosed seizures and 109 control subjects were enrolled. TLR-4 Asp299Gly and Thr399Ile polymorphisms and serum MMP-9 levels were evaluated. The patients were followed for 1 year.Asp/Gly (P = 0.012) and Thr/Ile (P = 0.002), Gly (Asp/Gly plus Gly/Gly) (P = 0.008) and Ile (Thr/Ile plus Ile/Ile) (P = 0.003) genotypes were significantly associated with calcified neurocysticercosis compared with controls. Gly/Gly and Ile/Ile genotypes were not significantly associated (P = 0.529 for Gly/Gly, P = 0.798 for Ile/Ile) with either group. The levels of MMP-9 were higher in calcified neurocysticercosis (P = < 0.001). The levels of MMP-9 were higher in patients with multiple calcified neurocysticercosis compared with single calcified neurocysticercosis (P = < 0.001).Headache (P = 0.031), status epilepticus (P = 0.029), Todd paralysis (P = 0.039), lesion size >10 mm (P = 0.001), and perilesional edema (P = < 0.001) were significantly associated with seizure recurrence. Heterozygous form Asp/Gly (P = < 0.001) and heterozygous form Thr/Ile (P = < 0.001) were significantly associated with seizure recurrence. The Gly (Asp/Gly plus Gly/Gly) (P = < 0.001) and Ile (Thr/Ile plus Ile/Ile) (P = < 0.001) genotypes were also significantly associated with seizure recurrence. Higher serum MMP-9 levels were significantly associated with seizure recurrence (P = < 0.001).The TLR-4 gene abnormalities may trigger inflammation around calcified neurocysticercosis leading to an increase in perilesional edema and provocation of seizures.

Guillain–Barré syndrome in Bangladesh: The role TLR4 Asp299Gly and Thr399Ile polymorphisms

Guillain–Barré syndrome in Bangladesh: The role TLR4 Asp299Gly and Thr399Ile polymorphisms

TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?

Background: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). Methods: DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA. Results: For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group (p = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10–0.62, p = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 μg/mL) were reduced when compared to reference value. Conclusions: The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals.

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.

Altered Th17 Cytokine Expression in Helicobacter pylori Patients with TLR4 (D299G) Polymorphism

ABSTRACTHelicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. However, the details and association with different polymorphism and clinical expression of infection remain unclear. A case-control study consisting of 58 patients with H. pylori infection and 44 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4 Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mucosal cytokines expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. The expression of IL-6, IL-17, IL-21, IL-23 and TGF-β1 was significantly higher in patients with D299G polymorphism in TLR4. But the expression of IL-18 between patients with single-nucleotide polymorphisms (SNPs) in TLR4 and patients with the wild-type allele was not significant. In H. pylori-infected patients with gastritis, SNPs in TLR4 may alter cytokine expression toward Th17 immune response in the gastric mucosa and may have increased risk for the development of peptic ulcer.

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Toll-like receptors (TLRs) 2 and 4 specifically recognize lipopolysaccharide motifs on surfaces of microorganisms. Polymorphims in the TLR genes result in structural variations in the proteins, abnormal host-pathogen interactions and hence, altered immune response. Opportunistic parasite Cryptosporidium spp. infects immuno-compromised patients who present with heterogeneous clinical manifestations ranging from mild infection resolving in a few weeks, to severe form characterized by voluminous diarrhoea, prolonged symptoms and recurrences. The present study investigates the role of TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms in pathogenesis of cryptosporidiosis. Stool samples were collected from 210 immuno-compromised (renal transplant recipients and patients with Human immunodeficiency virus infection) both with and without cryptosporidiosis, and 200 healthy subjects for detection of Cryptosporidium spp. Blood samples were also collected from the patients and healthy subjects for genotyping of Δ22 (TLR2 196_174del) polymorphism, A896G (TLR4 Asp299Gly) and C1196T (Thr399Ile) single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cryptosporidium spp. was detected in 70 immunocompromised patients, while it was absent in all the healthy controls. No significant difference was observed in Δ22, A896G and C1196T alleles and genotypes (P > 0.05), between cases and controls. Thus, TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms are not significantly associated with the pathogenesis or progression of cryptosporidiosis, in the Indian population included in the study.

Association of Toll-like receptors 2, 3, and 4 genes polymorphisms with periapical pathosis risk.

BackgroundThe aim of this study was to investigate the role of gene variations of Toll-like receptors (TLR) 2, 3, and 4 on genetic susceptibility to periapical pathosis.Material and MethodsOne hundred patients were included in the study and divided into two groups as follows; Control Group (n=50) that have root canal treatment and no periapical lesion, Patient Group (n=50) that have root canal treatment and periapical lesion. TLR2 Arg753Gln, TLR3 (c.1377C/T) and TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped by using PCR-RFLP. Genotypical analysis of control and patient groups were investigated to disclose whether there is any association between periapical lesions and gene variations.ResultsThere are no significant statistical differences between control and patient groups according to TLR 2 and 4 gene sequence. On the contrary, CC allele detected 74% for TLR 3 in patient group, and this difference was found to be statistically significant (p < 0.005).ConclusionsAccording to these results, it can be suggested that patients with Toll-like receptor 3 gene polymorphisms could be susceptible to periapical pathosis. Key words:Toll-like receptors, periapical pathosis, endodontics.

Toll-like receptor–4 gene polymorphisms in Javanese aggressive and chronic periodontitis patients

Background: Tool-like receptor-4 ( TLR4) gene polymorphisms affect the ability of the host in response to pathogenic bacteria, and can also be associated with the severity of periodontitis. TLR4 gene polymorphisms (Asp299Gly and Thr399Ile) are ones of gene mutations that occur in patients with aggressive periodontitis. Purpose: To investigate the involvement of TLR4 gene polymorphism as a risk factor of aggressive and chronic periodontitis of Javanese population in Surabaya. Method: This research can be considered as an analytic observational study, with a case-control study design in patients with aggressive periodontitis and chronic periodontitis. DNA samples were derived from peripheral blood. TLR4 gene polymorphisms (Asp299Gly and Thr399Ile) were then observed by PCR-RFLP. Result: There was no TLR4 gene polymorphism (Asp299Gly) in the whole samples. And, based on the results of simple logistic regression analysis on TLR4 gene polymorphisms (Thr399Ile), mutants heterozygote and homozygote obtained had OR value about 0.25. Conclusion: In Surabaya, there was no heterozygote and homozygote mutant in TLR4 gene polymorphisms, (Asp299Gly) and (Thr399Ile), that can be considered as risk factors of chronic periodontitis.

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)