TLR4 Gene Polymorphisms Research Articles

TLR2 Gene Polymorphism and MicroRNA 301 gene Expression Level as a Signature for Hepatocellular Carcinoma in Egyptian Patients

TLR2 Gene Polymorphism and MicroRNA 301 gene Expression Level as a Signature for Hepatocellular Carcinoma in Egyptian Patients

Evaluation of toll-like receptors 2 and 4 polymorphism and intestinal microbiota in children with food allergies.

Mutual regulation between immune system and gut microbiota is achieved through several mechanisms including the engagement of toll-like receptors (TLRs) which is expressed on numerous cell types. In this study we aimed to explore the association between food allergies and TLR gene polymorphisms in association with gut microbiota. Toll-like receptors polymorphism frequencies and some bacteria in the gut microbiota in 130 infants aged 1-24 months with egg and/or milk allergy in a prospective cohort were compared with 110 non-food allergic controls. Four candidate polymorphisms (TLR2 rs1898830/rs5743708 and TLR4 rs4986790/rs4986791) were genotyped by allelic discrimination polymerase chain rection (PCR) method. Gut microbiota analysis was achieved by using high-throughput sequencing. The TLR4 rs4986790 (Asp299Gly) single nucleotide polymorphism (SNP) major/minor allele frequency was 0.788/0.212 in food allergy patients and 0.719/0.280 in controls (p=0.017). There was a statistically significant difference between groups in terms of genotype frequencies (AA, AG, GG). Gut microbiota analysis revealed increased Firmicutes phylum in stool of the patients with food allergy. Except for TLR4 rs4986791 (Thr399lle) allele, the other TLR polymorphisms were not associated with food allergies in children. When the bacteria in the intestinal microbiota and TLR2 and TLR4 gene polymorphisms were compared; we determined a statistically significant increase in Bifidobacterium concentration in the intestinal microbiota in TLR4 rs4986791 CT heterozygous genotype (p=0.004). This study demonstrated a partial role of TLR4 gene polymorphism and gut microbiota in the development of food allergies. Future work in this area will be required to clarify the roles of different microbial strains that modulate gut microbiota composition and function in conjunction with TLR transcription pathways.

Relationship of Toll-Like Receptors 2 and 4 Gene Polymorphisms with Essential Hypertension in Chinese Han Population

Objective: There are numerous studies suggesting that genetic polymor-phisms of inflammation factors Toll-like receptors 2 and 4 (TLR2, TLR4) might play a role in the pathophysiological process of hypertension. In this study, we evaluated the association in a sample of members of the Chinese Han population. Method: We selected four single nucleotide polymor-phisms (SNP) of TLR2 (rs3804099, rs3804100, rs7656411) and TLR4 (rs1927906) genes, and measured the distributions of genotypic and allelic frequencies in 1063 participants, including 391 essential hypertension pa-tients and 672 controls. Result: No significant differences in the genotypic and allelic frequencies of the four SNPs were detected between cases and controls. However, three haplotypes, CCG, TTG and TTT of TLR2, were significantly associated with a decrease in the risk of essential hyperten-sion (OR: 0.512, 95% CI: 0.397 - 0.660, P P = 0.0038; OR: 0.797, 95% CI: 0.667 - 0.952, P = 0.0122, respectively). Inversely, the risk of essential hypertension increased sig-nificantly in patients with the CTG, TCG or TCT haplotypes (OR: 2.924, 95% CI: 2.157 - 3.963, P P P TLR2 might have profound effects on the development of essential hypertension in the Chinese Han population.

Association of TLR2 and TLR9 gene polymorphisms with atopic dermatitis: a systematic review and meta-analysis with trial sequential analysis

Atopic dermatitis (AD) is a chronic, inflammatory skin disease. The mechanism was complex. Genetic mutations of Toll-like receptor (TLR) may be associated with AD, yet still unclear. We aim to provide specific evidence of the association of TLR2, TLR9 gene polymorphisms with AD. Publications were selected according to the criteria. Newcastle-Ottawa Scale was applied to evaluate the quality. The value of ORs and 95%CIs were applied to measure the associations. According to the heterogeneity, the effects model of fixed or random was selected in data combination. For TLR2 gene rs5743708 polymorphism, under allele and recessive contrasts, the pooled data showed a significant correlation, which was A vs a, OR = 0.51 (95%CI: 0.30, 0.86); AA vs Aa + aa, OR = 0.54 (95%CI: 0.33, 0.88). For TLR2 gene rs4696480 polymorphism, under allele, homozygous, heterozygous, and dominant contrasts, the pooled data showed a significant correlation, which was A vs a, OR = 0.79 (95%CI: 0.64, 0.97), AA vs aa, OR = 0.65 (95%CI: 0.43, 0.97), Aa vs aa, OR = 0.68 (95%CI: 0.48, 0.97), AA + Aa vs aa, OR = 0.67 (95%CI: 0.49, 0.93). There are significant associations of TLR2 gene rs5743708, rs4696480 polymorphisms with atopic dermatitis, while no associations are found in TLR9 gene rs5743836, rs187084 polymorphisms.

Polymorphisms in toll-like receptor 3 and 4 genes as prognostic and outcome biomarkers in melanoma patients.

Melanoma is one of the most aggressive tumors, and in the setting of rising incidence and mortality, there is an urgent need to identify new prognostic markers. Toll-like receptors (TLRs), are aberrantly expressed in numerous cancers, including melanoma. TLR signaling provides a microenvironment that is involved in antitumor immune response, chronic inflammation, cancer cell proliferation and evasion of immune destruction. In the present study, we investigated whether single nucleotide polymorphisms (SNPs) in TLR3 and TLR4 genes are associated with clinicopathologic features, progression and survival of melanoma patients. The study was conducted on 120 melanoma patients. DNA extracted from peripheral blood was genotyped for TLR3 polymorphisms rs5743312 and rs3775291 (L412F) and TLR4 polymorphisms rs4986790 (D299G) and rs4986791 (T399I), by TaqMan Real-Time PCR Assays. Kaplan-Meier survival curves were compared by the log-rank test. TLR3 polymorphism L412F was associated with a higher mitotic index ( P = 0.035). TLR4 D299G and T399I polymorphisms were associated with indicators of melanoma severity, nodal metastases ( P = 0.005 and P = 0.007, respectively) and advanced stage III ( P = 0.005 and P = 0.004, respectively). Cox regression analysis showed that the presence of tumor-infiltrating lymphocytes (TILs) predicted better overall survival (HR = 0.318; P = 0.004). TLR4 T399I polymorphism was significantly associated with worse survival, P = 0.025. The overall survival rates were significantly lower for patients carrying variant allele T of TLR4 T399I SNP (TC and TT genotypes combined) ( P = 0.008, log-rank test), compared to wild-type genotype CC. Our findings indicate that TLR4 polymorphisms T399I (rs4986791) and D299G (rs4986790) could be potential prognostic and survival markers for melanoma patients.

Toll-Like Receptor 4 Gene Polymorphisms and Susceptibility to Schizophrenia: A Case-Control Study

ABSTRACT Schizophrenia is a common psychiatric disorder that exhibits a variety of symptoms. The exact etiology and pathogenesis are still doubtful. However, genetic and environmental factors seem to have a role. Years ago, the role of the immune system was focused on auto-antibodies, cytokines, different types of immune cells and immune genes. The Toll-like receptors (TLR) are a cornerstone of the innate immune system, particularly TLR4. TLR4 primarily recognises gram-negative lipopolysaccharides bacteria. This case-control study, for the first time to our knowledge, examined the role of TLR4 gene polymorphisms in 142 Egyptian schizophrenic patients and 175 healthy controls. Using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP), four single nucleotide polymorphisms (SNPs) were investigated in the TLR4 gene rs11536889, rs10759931, rs1927911, and rs1927914. The Positive and Negative Syndrome Scale (PANSS) was used in diagnosis and assessment. A statistically significant association was observed between rs11536889, rs1927911 and rs1927914, but no association was found between rs10759931. There was no association between the different SNP genotypes and PANSS, except between rs1927914 and general psychopathologic symptoms. This study shows a strong association between TLR4 rs11356889 and rs1927911 minor alleles and schizophrenia. These findings could be additional evidence for the immune system’s role in schizophrenia development. However, more studies with a more significant sample number, TLR4 protein assessment, and a larger number of SNPs are recommended.

TLR Signaling Pathway Gene Polymorphisms, Gene-Gene and Gene-Environment Interactions in Allergic Rhinitis.

ABSTRACTBackgroundAllergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene–gene and gene–environment interactions in AR.MethodsA total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case–control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene–gene and gene–environment interactions.ResultsIn the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene–gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene–environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction.ConclusionThe genetic polymorphisms of TLR2 and CD14 and gene–gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene–environment interactions and AR.

TLR4 Gene Polymorphisms Interaction With Ascaris Infection in Severe RSV Bronchiolitis.

IntroductionThe identification of gene-environment interactions allows the recognition of groups with higher risk of morbidity. This study evaluated the interaction between the presence of TLR4 gene polymorphisms and Ascaris infection with severe bronchiolitis in a tropical Colombian region.MethodsWe included all infants younger than 24 months hospitalized due to bronchiolitis in Hospital centers in the county of Rionegro, Colombia. To identify interaction between severe bronchiolitis and presence of TLR4 polymorphisms and Ascaris infection, we used log-binomial regression.ResultsFour hundred and seventeen infants were hospitalized due to bronchiolitis, of which 115 (27%) had severe bronchiolitis. In infants with respiratory syncytial virus (RSV) acute infection and positive anti-Ascaris IgE, TLR4 Asp299Gly was associated to low risk of severe bronchiolitis (OR 0.09, CI 95% 0.01–0.48). Conversely, in infants RSV negative with negative anti-Ascaris IgE, TLR4 Asp299Gly was associated with an increased risk of severe bronchiolitis (OR 14.5, CI 95% 2.2–96).ConclusionIn our population there is an interaction between the presence of severe bronchiolitis, TLR4 Asp299Gly and Ile399Thr polymorphisms, anti-Ascaris IgE levels and RSV. This association should be evaluated in other populations to elucidate its role in the pathogenesis of severe bronchiolitis.

The role of TLR-2 and TLR-4 gene polymorphisms in the development of sepsis in children with severe burns

Recently, many studies are based on the study of innate immunity genes, namely the role of TLRs in the development of various diseases. Severe burn injury is characterized by the development of hyperimmune reactions, which further leads to the development of multiple organ complications and sepsis. The aim of our study was to identify the frequency and prognostic value of polymorphism of TLR-2 Arg753Gln and TLR-4 Thr399 Ile genes and their role in the development of sepsis and MOD in children with severe burns. Materials and methods: genetic analysis of TLR-2 Arg 753 Gln and TLR-4 Thr399 Ile gene polymorphisms was performed in children with severe and extremely severe burns (n ​​= 22) who were treated in the anesthesiology department with intensive care beds. Results: as a result of the obtained data, the heterozygous genotype TLR-2 Arg 753 Gln was detected in 69.5% (n = 16), in 31.8% (n = 7) patients with burn injury polymorphism was not detected. In 13.6% (n = 3) cases, polymorphism was associated with sepsis and MOD. Sepsis and normal homozygous genotype were diagnosed in 4.5% (n = 1). Heterozygous genotype TLR-4 Thr399 Ile was observed in 18.2% (n = 4) patients, of which only 4.5% (n = 1) patients had polymorphism associated with sepsis and MOD. Analysis of the association of TLR 2 genotypes and markers of acute inflammation revealed statistically significant differences between the heterozygous TLR 2 Arg 753 Gln genotype and C-reactive protein (CRP) levels in the blood of patients on day 3 of burn disease. Conclusions: The study of the role of innate immune system genes is promising in predicting the development of sepsis and complications in severe burns and requires further careful study.

TLR4 polymorphisms as potential predictors of atopic dermatitis in Chinese Han children.

BackgroundToll‐like receptor 4 (TLR4) is considered to be involved in the pathogenesis and progression of atopic dermatitis (AD). In the present study, we evaluated the relationship between TLR4 gene polymorphisms and the susceptibility or severity of AD among Chinese Han children.MethodsA total of 132 AD patients and 100 healthy controls were enrolled in this study. Four single‐nucleotide polymorphisms (rs19277914, rs11536891, rs7869402, and rs11536889) of the TLR4 gene were genotyped by multiplex PCR combined with next‐generation sequencing.ResultsOur results showed that a significantly reduced risk for AD was associated with C allele [p = 0.008; odds ratio (OR) = 0.41, C vs. T], TC genotype (p = 0.022; OR = 0.41, TC vs. TT), and TC + CC genotype (p = 0.010; OR = 0.39, TC + CC vs. TT) of TLR4 rs11536891. The frequency of the haplotype GCCG (rs1927914–rs11536891–rs7869402–rs11536889) in AD patients was lower than that in the controls (p = 0.010; OR = 0.38). Moreover, the results indicated that a higher risk of severe AD was related to the T allele (p = 0.019; OR = 2.97, T vs. C) and the TC genotype (p = 0.021; OR = 3.34, TC vs. CC) of TLR4 rs7869402. A risk haplotype of TLR4 (GTTG) was found in severe AD patients (p = 0.010; OR = 5.26).ConclusionsOur data suggested that TLR4 rs11536891 polymorphism was associated with the susceptibility to AD in Chinese Han children. And TLR4 rs7869402 might confer the severity of pediatric AD patients.

TLR2, as a Pathogen Recognition Receptor, Plays Critical Roles in Hepatitis B Outcome.

The immune system of active and inactive chronic hepatitis B, as prolonged forms of hepatitis B, is unable to eradicate hepatitis B virus (HBV) from the infected hepatocytes completely. Toll-like receptors (TLRs) play key roles in the viral recognition and promotion of appropriate immune responses. The molecules also participate in the alteration of the target cell functions and transformation. TLR2 is the unique molecule that makes either homodimer or heterodimer with TLR1 and 6 and shows variable roles against viral infections. Therefore, it has been hypothesized that TLR2 may participate in both immune response against HBV and induction of the virus-related hepatic complications. The studies confirm the hypothesis and revealed that TLR2 is not only one of the main molecules altering the course of HBV infection, but also plays key roles in induction of hepatocellular carcinoma (HCC) and liver cirrhosis. However, recent studies demonstrated that the molecule can fight against HCC and liver cirrhosis. Collectively, it appears that nutrition habits, TLR2 gene polymorphisms, gut microbiome, HBV antigens, and activation of other receptors may play key roles in the determination of TLR2 functions.

Toll-Like Receptor-4 Gene (Asp299Gly) polymorphism in allergic conjunctivitis

Allergic conjunctivitis (AC) is an allergic reaction that causes inflammation of the conjunctiva. Toll-like receptors (TLRs) are essential innate immune receptors that contribute to developing various allergic diseases. This case-control study aims to determine the correlation between TLR-4 gene (Asp299Gly) polymorphism and AC incidence and severity. The study included 70 AC patients and 70 non-allergic controls. All included subjects were subjected to a skin prick test, total immunoglobulin E (IgE) measurement, and TLR-4 gene (Asp299Gly) polymorphism detection by PCR restriction fragment length polymorphism (PCR-RFLP) technique. AC patients had significantly higher total IgE levels than controls (P ≤ 0.001). The frequency of the wild-type AA and heterozygous AG genotype were significantly lower in AC patients compared to controls (60 % vs. 80 % and 8.6% vs. 12.9 %, respectively). In contrast, the homozygous mutant GG genotype was significantly more prevalent among AC patients than controls (31.4 % vs. 7.1 %). Furthermore, the wild AA genotype was strongly associated with mild disease (68.2%); nonetheless, the homozygous mutant GG genotype was linked to severe disease (53.8%). The heterozygous AG genotype was only found in moderate AC patients (17.1%). AC patients with the mutant G allele may be more likely to have a severe course of AC.

Association of TLR 9 gene polymorphisms with remission in patients with rheumatoid arthritis receiving TNF-\u03b1 inhibitors and development of machine learning models

Toll-like receptor (TLR)-4 and TLR9 are known to play important roles in the immune system, and several studies have shown their association with the development of rheumatoid arthritis (RA) and regulation of tumor necrosis factor alpha (TNF-α). However, studies that investigate the association between TLR4 or TLR9 gene polymorphisms and remission of the disease in RA patients taking TNF-α inhibitors have yet to be conducted. In this context, this study was designed to investigate the effects of polymorphisms in TLR4 and TLR9 on response to TNF-α inhibitors and to train various models using machine learning approaches to predict remission. A total of six single nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was used to investigate the association between genetic polymorphisms and response to treatment. Various machine learning methods were utilized for prediction of remission. After adjusting for covariates, the rate of remission of T-allele carriers of TLR9 rs352139 was about 5 times that of the CC-genotype carriers (95% confidence interval (CI) 1.325–19.231, p = 0.018). Among machine learning algorithms, multivariate logistic regression and elastic net showed the best prediction with the area under the receiver-operating curve (AUROC) value of 0.71 (95% CI 0.597–0.823 for both models). This study showed an association between a TLR9 polymorphism (rs352139) and treatment response in RA patients receiving TNF-α inhibitors. Moreover, this study utilized various machine learning methods for prediction, among which the elastic net provided the best model for remission prediction.

TLR4 gene polymorphisms in Egyptian vitiligo patients: insights into emerging association with clinical activity, family history, and response to therapy

BackgroundVitiligo is a common pigmentary disorder in which autoimmunity has been suggested to play an important role. Toll-like receptor (TLR) family are recognized different molecular structures expressed on immune cells and have been implicated in a number of autoimmune diseases (AIDs) such as vitiligo. The purpose of this study was to investigate the possible association between TLR4 gene polymorphisms: rs11536858, rs1927911, rs1927914 in Egyptian vitiligo patients and their clinical data, their response to therapy. Using PCR-RFLP for TLR4 gene polymorphisms (rs11536858, rs1927911, and rs1927914), both alleles and genotypes were determined after extraction of DNA in a case-control study of 100 vitiligo Egyptian patients and 100 matched age and sex controls. ResultsThe distribution of the protective CT genotype of rs1927914 was higher in the control group. After dividing both patients and controls into 2 age groups (below 18 and above 18 years), no significant associations between the genotypes of the selected TLR4 SNPs and the demographic and clinical data of the vitiligo patients in group 1 (below 18 years) were observed. For group 2 (above 18 years), also no significant associations were found except for the association between the CC genotype of rs1927914 and psychiatric trauma, from one side, and between the CT genotype of rs1927911 and alopecia, from the other side. The association between combined genotypes and the risk of vitiligo showed either higher frequency in patients (risky), or controls (protective), and some equal frequencies (non-significant). The association between haplotypes and risk of vitiligo in patients’ group revealed the highest frequency for the risky ATT and the least frequency for ATC haplotypes. In control group, the protective GCT haplotype showed the highest frequency while the GTC and GCC showed the least frequency. No significant correlations of haplotypes with clinical and demographic data of selected patients’ group were observed apart from that between ACC haplotype and family history of AIDs and between ATT haplotype and remission after phototherapy. ConclusionsThe significant relationship between TLR4 gene polymorphisms and vitiligo patients charcteristics clarify the role of innate immunity in pathogensis of vitiligo and its effect on the used therapies.

Influence of TLR4 and TLR9 polymorphisms and haplotypes on multiple hrHPV infections and HPV16 copy number in cervical cancer and cervicitis

Genetic polymorphism in pathogen recognition receptors tends to influence infection, disease susceptibility, and progression. We analyzed the association of TLR4 and TLR9 gene polymorphisms with multiple hrHPV infections and HPV16 copy number in cervicitis and cervical cancer. A total of 440 cervical cancer, cervicitis, and healthy individuals were studied using PCR-based assays. Student t-test, chi-square test, Welch's t-test, and Fisher's Exact test were utilized to evaluate the association of HPV infection with polymorphisms. Haploview and FAMHAP were used to analyze haplotype association with HPV infection and viral load. Study results revealed HPV45 infection as the most common one in cervical cancer after HPV16, and one-fourth HPV positive cervical cancer patients possessed multiple HPV infections. Mean HPV16 copy number of 264.4 ± 58.7 and 2.1 ± 3.3 copies/cell was detected in cervical cancer and cervicitis, respectively. TLR4 rs10759931 was protective against multiple hrHPV infections. TLR4 haplotype ACAC was associated with an increased risk of multiple hrHPV infections. TLR9 SNPs rs187084, rs352140, and rs352139 were associated with decreased risk of high HPV16 copy number. Augmentation of efforts for the multivalent HPV vaccination in India is suggested. The analyzed polymorphisms were shown to modulate hrHPV co-infections and HPV16 viral load that warrants further analysis.

Prevalence of Allelic and Genotypic Variants of Il4, Il10, Il12b and Tlr2 Gene Polymorphism in Patients with Chronic Polypoid Rhinosinusitis

Chronic polyposis rhinosinusitis (CPRS) is an important medical and social problem due to its prevalence, combination with other diseases (bronchial asthma, cystic fibrosis), prolonged recurrent course, which leads to a decrease in the quality of life and performance of patients. Bronchopulmonary, rhinogenic orbital and intracranial complications arising against the background of chronic sinusitis not only worsen the quality of life of patients, but also sometimes lead to long-term disability, and sometimes to disability. The results of our study demonstrated that the distribution of the genotypes of polymorphisms of all genes corresponded to the expected, i.e., in this case, the Hardy-Weinberg equilibrium is fulfilled in both groups. Both samples rs2243250 of the IL4 gene were characterized by high frequencies of the unfavorable C allele and the heterozygous T / C genotype, rs3212227 of the IL12B gene of the A allele and the heterozygous A / C genotype, rs1800895 592 C> A in the IL10 gene of the A, C alleles, and heterozygous C rs5743708 in the TLR2 gene of the C allele and the heterozygous C / T genotype, hence the high level of genetic variability of the studied genes.

Prevalence of Allelic and Genotypic Variants of Il4, Il10, Il12b and Tlr2 Gene Polymorphism in Patients with Chronic Polypoid Rhinosinusitis

Chronic polyposis rhinosinusitis (CPRS) is an important medical and social problem due to its prevalence, combination with other diseases (bronchial asthma, cystic fibrosis), prolonged recurrent course, which leads to a decrease in the quality of life and performance of patients. Bronchopulmonary, rhinogenic orbital and intracranial complications arising against the background of chronic sinusitis not only worsen the quality of life of patients, but also sometimes lead to long-term disability, and sometimes to disability. The results of our study demonstrated that the distribution of the genotypes of polymorphisms of all genes corresponded to the expected, i.e., in this case, the Hardy-Weinberg equilibrium is fulfilled in both groups. Both samples rs2243250 of the IL4 gene were characterized by high frequencies of the unfavorable C allele and the heterozygous T / C genotype, rs3212227 of the IL12B gene of the A allele and the heterozygous A / C genotype, rs1800895 592 C> A in the IL10 gene of the A, C alleles, and heterozygous C rs5743708 in the TLR2 gene of the C allele and the heterozygous C / T genotype, hence the high level of genetic variability of the studied genes.

Ornithine decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus.

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI: 2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p = 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer in univariate models as well as models adjusted for age, sex, and CagA serostatus. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 × 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the T allele at rs1927914.

The frequency of TLR2 (rs3804099, rs3804100, and rs5743708) and TLR4 (rs4986790 and rs4986791) polymorphisms in women with polycystic ovary syndrome – preliminary study

Introduction Low-grade chronic inflammation may participate in PCOS etiology. Toll-like receptors (TLRs) may play a pivotal role in the initiation and progression of inflammatory process. We examined TLR2 and TLR4 gene polymorphisms in women with PCOS and their associations with metabolic/hormonal parameters. Material and methods Sixty-eight women qualified for the study. PCOS was diagnosed in 40 women. The control group consisted of 28 women. All patients underwent anamnesis, physical examination, anthropometric measurements, and biochemical/hormonal assessments. The TLRs gene polymorphism was tested using PCR and the minisequencing method. Results The frequency of TLR2 gene polymorphisms genotypes (rs3804099, rs3804100, and rs5743708) did not differ significantly between the groups. The difference in frequency of genotypes of TLR4 gene polymorphisms (rs4986790 and rs4986791) was close to the statistical significance level. No significant correlations between TLR2/TLR4 polymorphisms and anthropometric/metabolic parameters in PCOS group were observed. However, the relationship between HDL concentration and TLR2 S450S (rs3804100) polymorphism was close to the statistical significance level. Positive correlations between the two TLR4 polymorphisms (rs4986790 and rs4986791) were found, as well as between the TLR2 S450S (rs3804100) gene polymorphism and FSH concentration. Conclusions The TLR4 gene polymorphism may play a role in the PCOS etiopathogenesis but this observation needs further investigation.

TLR3 polymorphisms are associated with the severity of hand, foot,and mouth disease caused by enterovirus A71 in a Chinese children population.

Hand, foot,and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816, and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889, and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323, and rs5741880), and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879, and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single-nucleotide polymorphism rs1879026 had a higher risk of developing severe cases (GG vs. GT: OR = 1.875; 95% CI, 1.183-2.971; p = .007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs. CT: OR = 0.350; 95% CI, 0.163-0.751; p = .006; C vs. T: OR = 0.566; 95% CI, 0.332-0.965; p = .036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs. CT: OR = 2.537; 95% CI, 1.108-5.806; p = .026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs. GT: OR = 2.076; 95% CI, 1.144-3.768; p = .016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290, and rs3775291 are associated with the severity of EV-A71-associated HFMD in a Chinese children population.