Absence of toll-like receptor 9 Pro99Leu polymorphism in cervical cancer.
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ABSTRACT:
SUBMITTER: Chauhan A
PROVIDER: S-EPMC6171715 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The role played by the polymorphism located in Toll-like Receptor 9 (TLR9) as a risk factor of cervical cancer remains elusive. Therefore, we studied the association of the TLR9 -1486 T/C (rs187084) and C2848T (rs352140) polymorphisms with cervical cancer. The TLR9 -1486 T/C and C2848T polymorphism was genotyped in 426 patients and 460 unrelated healthy females from the Polish population. Logistic regression analysis adjusting for age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal status showed that both the TLR9 -1486 T/C and C2848T polymorphisms could be a genetic risk factor for cervical cancer. For the TLR9 -1486 T/C polymorphism, the adjusted OR for patients with the C/T genotype versus T/T genotype was 1.371 (95 % CI 1.021-1.842, p = 0.0361), the adjusted OR for the C/C genotype vs the T/T genotype was 1.300 (95 % CI 1.016-1.507, p = 0.0096), and the adjusted OR for the C/T or C/C genotype vs the T/T genotype was 1.448 (95 % CI 1.099-1.908, p = 0.0083). For the C2848T polymorphism, the adjusted OR for patients with the C/T genotype vs C/C genotype was 1.443 (95 % CI 1.019-2.043, p = 0.0380), the adjusted OR for the T/T genotype vs the C/C genotype was 1.237 (95 % CI 1.016-1.507, p = 0.0328), and the adjusted OR for the T/C or T/T genotype vs the C/C genotype was 1.345 (95 % CI 0.976-1.855, p = 0.0700). Our studies suggest that the TLR9 -1486 T/C and C2848T polymorphisms may be a genetic risk factor for cervical cancer.
| S-EPMC3383973 | biostudies-literature
Project description:Polymorphism in the Toll-like receptor (TLR) 9 gene has been shown to have a significant role in some diseases; however, little is known about its possible role in the natural history of human papillomavirus (HPV) infections. We investigated the association between a single-nucleotide polymorphism (SNP) (rs5743836) in the promoter region of TLR9 (T1237C) and type-specific HPV infections. Specimens were derived from a cohort of 2462 women enrolled in the Ludwig-McGill Cohort Study. We randomly selected 500 women who had a cervical HPV infection detected at least once during the study as cases. We defined two control groups: (i) a random sample of 300 women who always tested HPV negative, and (ii) a sample of 234 women who were always HPV negative but had a minimum of ten visits during the study. TLR9 genotyping was performed using bidirectional PCR amplification of specific alleles. Irrespective of group, the WT homozygous TLR9 genotype (TT) was the most common form, followed by the heterozygous (TC) and the mutant homozygous (CC) forms. There were no consistent associations between polymorphism and infection risk, either overall or by type or species. Likewise, there were no consistently significant associations between polymorphism and HPV clearance or persistence. We concluded that this polymorphism in the promoter region of TLR9 gene does not seem to have a mediating role in the natural history of the HPV infection.
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Project description:Toll-like receptor 5 (TLR5) plays a fundamental role in immune responses. Recent findings suggest the TLR5 expression level affects cancer progression and development. In the present study, our examination of 256 breast carcinomas specimens revealed that TLR5 is overexpressed in breast carcinomas, and that TLR5 overexpression correlated with lymph node metastasis and cancer grade (p<0.01). In a case-control study, we also analyzed associations between TLR5 single nucleotide polymorphisms (SNPs) and breast cancer risk. Compared were 516 Chinese Han women diagnosed mainly with infiltrative ductal carcinoma and 520 age-matched healthy controls. The nonsense SNP rs5744168 causes truncation of the TLR5 transmembrane signaling domain and was associated with breast cancer risk (p<0.05). However, no statistical association was detected between SNP rs5744168 and any of the clinical parameters tested. Our findings thus indicate that TLR5 SNP rs5744168 is associated with sporadic breast cancer occurrence.
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Project description:This meta-analysis systematically reviews the association between Toll-like receptor 9 polymorphisms and the risk of cervical cancer. Case-control studies focused on the association were collected from the PubMed, Web of Science, Cochrane Library, Embase, MEDLINE, CNKI, VIP, and Wanfang databases from inception to July 2017. We screened the studies and assessed the methodological quality of the included studies and extracted data. A meta-analysis was performed using RevMan 5.3 and Stata 12.0 software. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the associations between Toll-like receptor 9 polymorphisms and cervical cancer risk. A total of 9 studies comprising 3331 cervical cancer patients and 4109 healthy controls met the inclusion criteria. Of these, 8 studies contained information about G2848A (rs352140) and 4 studies contained information about -1486T/C (rs187084). Our results revealed that the associations between rs187084 and cervical cancer risk in the dominant model (p = 0.002) and heterozygous model (p = 0.002) were significant, with 1.30- and 1.32-fold increases in susceptibility, respectively, compared to that in the wild-type model. However, rs352140 was not related to cervical cancer regardless of whether the subgroup analysis was conducted (p > 0.05). In conclusion, there is a significant correlation between rs187084 and cervical cancer risk with the minor C allele increasing the risk of occurrence of cervical cancer. However, rs352140 is not associated with the occurrence of cervical cancer.
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Project description:DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.
| S-EPMC1282462 | biostudies-literature
Project description:Innate immune signals mediated by Toll-like receptors (TLRs) have been thought to contribute considerably to the antibody-enhancing effects of vaccine adjuvants. However, we report here that mice deficient in the critical signaling components for TLR mount robust antibody responses to T cell-dependent antigen given in four typical adjuvants: alum, Freund's complete adjuvant, Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate adjuvant. We conclude that TLR signaling does not account for the action of classical adjuvants and does not fully explain the action of a strong adjuvant containing a TLR ligand. This may have important implications in the use and development of vaccine adjuvants.
| S-EPMC1868398 | biostudies-literature
Project description:The objective was to assess the impact of genetic variation on cervical cytokine concentrations of interleukin (IL)-1?, IL-1?, IL-6, IL-8 and tumor necrosis factor alpha (TNF-?), and first, to determine if these variants interact with polymorphisms in Toll-like receptor 4 (TLR4) that were previously shown to associate with pro-inflammatory cervical cytokine concentrations, and second, to determine if findings are affected by bacterial vaginosis (BV). We examined 183 single nucleotide polymorphisms (SNPs) in 13 cytokine genes and receptors for associations with cervical cytokine levels in 188 African American and European American women. We tested for associations of gene-gene interactions between SNPs in TLR4 and cytokine gene and receptor polymorphisms with cervical pro-inflammatory cytokines. None of the single locus associations were significant after correction for multiple testing in either European Americans or African Americans. However, there were significant gene-gene interactions between IL-1R2 rs485127 and two SNPs in TLR4 (rs1554973 and rs7856729) with IL-1? after correction for multiple testing. Our study demonstrates that interactions between TLR4 and IL-1R2 are associated with cervical pro-inflammatory cytokine concentrations. These results provide important insights into the possible regulatory mechanisms of the inflammatory response in the presence and absence of microbial disorders such as BV. Additionally, the observed differences in allele frequencies between African Americans and those of European descent may partially explain population disparity in pregnancy-related phenotypes that are cytokine concentration-dependent.
| S-EPMC3147278 | biostudies-literature
Project description:Ovarian cancer (OC) is one of the most common cancers threatening women's lives around the world. Epithelial ovarian tumors represent the most common ovarian neoplasms. Most OC patients are diagnosed at the advanced stage, and there is an urgent need to identify novel biomarkers of the disease. Single-nucleotide polymorphisms (SNPs) in TLR genes may serve as crucial markers of cancer susceptibility. We investigated the frequency of TLR polymorphisms in a group of 200 women, including 70 with OC. Four SNPs, two each in TLR4 (rs4986790 and rs4986791) and TLR9 (rs187084 and rs5743836), were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The digested fragments were separated and identified by multicapillary electrophoresis. The load quantification of human papillomavirus (HPV) types 16/18 was determined using a digital droplet PCR method. We found an increased frequency of heterozygous genotype and minor allele of the TLR4 rs4986790 SNP in women with OC compared with healthy controls, and this result remained highly significant after Bonferroni's correction for multiple testing (p < 0.0001). No evidence of linkage disequilibrium was found with any of the examined TLR SNPs. The findings suggest that the TLR4 Asp299Gly polymorphism could be a genetic risk factor for the development of OC.
| S-EPMC9563956 | biostudies-literature
Project description:Toll-like receptors (TLRs) contribute to the immune response by recognizing patterns presented by bacteria and other pathogens. These receptors have been implicated in the inflammatory response that contributes to gingivitis and periodontitis. Conflicting reports have suggested that variations in the genes encoding TLRs, particularly TLR2 and TLR4, may influence susceptibility to periodontitis. In this study, the contribution of variations in the genes encoding TLR2 and TLR4 in the context of periodontitis was examined in 254 patients with moderate periodontitis, 418 patients with severe periodontitis, and 260 healthy controls free of gum disease. Genomic DNA was extracted from participants' whole blood, and genotyping of TLR2/TLR4 as performed using real-time polymerase chain reaction with TaqMan MGB primer. The genotype, allele, and haplotype frequencies were compared among control, moderate periodontitis, and severe periodontitis groups. Statistical analysis was performed using chi-square and logistic regression analyses. Of the 9 polymorphic loci detected in the two genes, one, rs11536889 (G>C) in TLR4, displayed a statistically significant difference in distribution between individuals with moderate periodontitis and severe periodontitis (P<0.05). The distribution of the GG genotype in moderate periodontitis was higher than in the severe periodontitis group (P<0.05). Further, for the haplotype rs7873784, rs1927907, and rs1153688 of TLR4, the distribution of haplotype GCG was statistically different between moderate periodontitis and severe periodontitis (P<0.05, OR=1.501). These findings indicate that variation in TLR4 may affect chronic periodontitis susceptibility in a Han Chinese population.
| S-EPMC4483984 | biostudies-literature
Project description:AIM:Periodontitis is a multifactorial disease, with microbial dental plaque as the primary etiological factor. However, the manifestation and progression of periodontitis is influenced by a wide variety of other determinants and factors such as social and behavioral factors, systemic factors, microbial composition of dental plaque, genetic, and many other emerging risk factors. The aim of this study was to analyze genetic polymorphisms in the toll-like receptor 9 (TLR9) gene at - 1237C/T and its association with chronic and generalized aggressive periodontitis (GAgP) in an Indian population. MATERIALS AND METHODS:This study was carried out on 90 subjects, which included 30 GAgP and 30 chronic periodontitis patients and 30 healthy controls. Within the limitations of our study, only 30 subjects were included in each group due to the low prevalence of GAgP patients. Blood samples were drawn from the subjects and analyzed for TLR9 genetic polymorphism at - 1237C/T by using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:No significant difference was found in genotype and allele frequency of TLR9 genetic polymorphism (- 1237C/T) in generalized aggressive and chronic periodontitis patients and healthy controls. CONCLUSION:Toll-like receptor 9 genetic polymorphism at - 1237C/T may not be associated with GAgP and chronic periodontitis patients in Indian population.
| S-EPMC4296456 | biostudies-literature