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

Sharma, Swati; Singh, Satyendra Kumar; Kakkar, Kavita; Nyari, Nikky; Dhole, Tapan N.; Kashyap, Rajesh; Hasan, Sadid A.

doi:10.1016/j.meegid.2016.06.027

Cited by 10 publications

(7 citation statements)

References 28 publications

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“…Compared to TLR4-rs4986790, the allelic and genotypic frequencies did not follow the Hardy Weinberg equilibrium. However, previous research in the Indian population shows that individuals with the heterozygous genotype for TLR4-rs4986790 and TLR4-rs4986791 polymorphisms had increased susceptibility to dengue infection and the IIe/Gly (TG) haplotype was associated with the risk of the disease [18]. However, a study from Indonesia showed that the distribution of the TLR4-rs4986790 and TLR4-rs4986791 polymorphisms did not differ between children with severe dengue case presentation (DHF/DSS) and controls [17].…”

Section: Discussionmentioning

confidence: 94%

“…A study conducted of children in Indonesia showed that the presence of the Asp299Gly and Thr399Ile SNPs in TLR4 favors the susceptibility to infection and the severity of dengue in this population [17]. A study conducted with adults in India showed that individuals heterozygous with Asp299Gly and Thr399Ile had greater susceptibility to dengue infection [18]. Likewise, the high frequency of the T allele of the SNP TLR3-rs3775291 in adults of India associated with DHF in comparison with DF has been reported.…”

Section: Introductionmentioning

confidence: 95%

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Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

Posadas-Mondragón

Aguilar-Faisal

Zúñiga

et al. 2020

Viruses

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Dengue manifestations range from a mild form, dengue fever (DF), to more severe forms such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The ability of the host to present one of these clinical forms could be related to polymorphisms located in genes of the Toll-like receptors (TLRs) which activate the pro-inflammatory response. Therefore, the genotyping of single nucleotide genetic polymorphisms (SNPs) in TLR3 (rs3775291 and rs6552950), TLR4 (rs2737190, rs10759932, rs4986790, rs4986791, rs11536865, and rs10983755), TLR7 (rs179008 and rs3853839), and TLR8 (rs3764880, rs5741883, rs4830805, and rs1548731) was carried out in non-genetically related DHF patients, DF patients, and general population (GP) subjects. The SNPs were analyzed by real-time PCR by genotyping assays from Applied Biosystems®. The codominance model showed that dengue patients had a lower probability of presenting the TLR4-rs2737190-G/G genotype (odds ratio (OR) (95% CI) = 0.34 (0.14–0.8), p = 0.038). Dengue patients showed a lower probability of presenting TLR4-rs11536865-G/C genotype (OR (95% CI) = 0.19 (0.05–0.73), p = 0.0092) and had a high probability of presenting the TACG haplotype, but lower probability of presenting the TGCG haplotype in the TLR4 compared to GP individuals (OR (95% CI) = 0.55 (0.35–0.86), p = 0.0084). In conclusion, the TLR4-rs2737190-G/G and TLR4-rs11536865-G/C genotypes and TGCG haplotype were associated with protection from dengue.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

Posadas-Mondragón

Aguilar-Faisal

Zúñiga

et al. 2020

Viruses

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“…These included studies are presented in Table 1 . The presence of the mutant allele of the SNP was associated with susceptibility to several infectious diseases: COVID-19 ( Taha et al, 2021 ); Escherichia coli infection ( Sampath et al, 2013 ); Orientia tsutsugamushi infection ( Janardhanan et al, 2013 ); S. pyogenes and H. influenzae ( Liadaki et al, 2011 ); mononucleosis ( Jabłońska et al, 2020 ); UTI in Indian diabetic patients ( Gond et al, 2018 ); dengue infection ( Sharma et al, 2016 ); influenza H1N1 in the Italian population ( Esposito et al, 2012a ); HBV/HCV ( Sghaier et al, 2019 ); HIV ( Vidyant et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

The relationship between 896A/G (rs4986790) polymorphism of TLR4 and infectious diseases: A meta-analysis

et al. 2022

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Toll-like Receptors (TLRs), such as the TLR4, are genes encoding transmembrane receptors of the same name, which induce a pro- or anti-inflammatory response according to their expression as the host’s first line of defense against pathogens, such as infectious ones. Single nucleotide polymorphisms (SNPs) are the most common type of mutation in the human genome and can generate functional modification in genes. The aim of this article is to review in which infectious diseases there is an association of susceptibility or protection by the TLR4 SNP rs4986790. A systematic review and meta-analysis of the literature was conducted in the Science Direct, PUBMED, MEDLINE, and SciELO databases between 2011 and 2021 based on the dominant genotypic model of this SNP for general and subgroup analysis of infectious agent type in random effect. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for genotypic comparison. I2 statistics were calculated to assess the presence of heterogeneity between studies and funnel plots were inspected for indication of publication bias. A total of 27 articles were included, all in English. Among the results achieved, the categories of diseases that were most associated with the SNP studied were in decreasing order of number of articles: infections by bacteria (29.63%); caused by viruses (22.23%); urinary tract infection—UTI (7.4%), while 11 studies (40.74%) demonstrated a nonsignificant association. In this meta-analysis, a total of 5599 cases and 5871 controls were finalized. The present meta-analysis suggests that there is no significant association between TLR4-rs4986790 SNP and infections (OR = 1,11; 95% CI: 0,75–1,66; p = 0,59), but in the virus subgroup it was associated with a higher risk (OR = 2,16; 95% CI: 1,09–4,30; p = 0,03). The subgroups of bacteria and parasites did not show statistical significance (OR = 0,86; 95% CI: 0,56–1,30; p = 0,47, and no estimate of effects, respectively). Therefore, it has been shown that a diversity of infectious diseases is related to this polymorphism, either by susceptibility or even severity to them, and the receptor generated is also crucial for the generation of cell signaling pathways and immune response against pathogens.

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“…However, there have been conflicting studies on the association of common human TLR4 polymorphisms (D299G and T399I) with symptomatic RSV infection in children ( Tal et al, 2004 ; Awomoyi et al, 2007 ; Paulus et al, 2007 ). Studies in the context of dengue infection have yielded similarly conflicting findings ( Djamiatun et al, 2011 ; Sharma et al, 2016 ; Posadas-Mondragón et al, 2020 ), while TLR4 polymorphisms D299G and T399I were associated with COVID-19 severity and cytokine storm ( Taha et al, 2021 ). The conflicting results from these studies may reflect small cohort sizes and differences in study populations.…”

Section: Future Directionsmentioning

confidence: 99%

Activation of TLR4 by viral glycoproteins: A double-edged sword?

et al. 2022

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Recognition of viral infection by pattern recognition receptors is paramount for a successful immune response to viral infection. However, an unbalanced proinflammatory response can be detrimental to the host. Recently, multiple studies have identified that the SARS-CoV-2 spike protein activates Toll-like receptor 4 (TLR4), resulting in the induction of proinflammatory cytokine expression. Activation of TLR4 by viral glycoproteins has also been observed in the context of other viral infection models, including respiratory syncytial virus (RSV), dengue virus (DENV) and Ebola virus (EBOV). However, the mechanisms involved in virus-TLR4 interactions have remained unclear. Here, we review viral glycoproteins that act as pathogen-associated molecular patterns to induce an immune response via TLR4. We explore the current understanding of the mechanisms underlying how viral glycoproteins are recognized by TLR4 and discuss the contribution of TLR4 activation to viral pathogenesis. We identify contentious findings and research gaps that highlight the importance of understanding viral glycoprotein-mediated TLR4 activation for potential therapeutic approaches.

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

Cited by 10 publications

References 28 publications

Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

Association of Genetic Polymorphisms in TLR3, TLR4, TLR7, and TLR8 with the Clinical Forms of Dengue in Patients from Veracruz, Mexico

The relationship between 896A/G (rs4986790) polymorphism of TLR4 and infectious diseases: A meta-analysis

Activation of TLR4 by viral glycoproteins: A double-edged sword?

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