Background: Toll-like receptors are central components of host defence in humans, responsible for recognition of pathogen-associated molecular patterns and activation of innate immunity. Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS) and other microbial components, thereby initiating the expression and release of pro-inflammatory cytokines. The common, frequently co-segregating allelic variants Asp299Gly and Thr399Ile have been related to susceptibility to gram-negative infections and sepsis and may be involved in the development of atherosclerosis. Identification of TLR4 Asp299Gly and Thr399Ile genotypes can be important for examination of genotype/phenotype relationships as well as for individual risk assessment of patients.
Methods: TLR4 Asp299Gly and Thr399Ile genotypes were detected by a single tube polymerase chain reaction (PCR), based on exonuclease degradation of dual labelled allele-specific oligonucleotides. The assay results were compared with conventional restriction fragment length polymorphism (RFLP) analysis.
Results: Genotypes of 345 individuals were determined simultaneously in a single PCR assay. Allele frequencies for our population were 6.8% for the TLR4 Asp299Gly polymorphism and 6.4% for the Thr399Ile polymorphism. Validation by RFLP analysis revealed a correct detection of all genotypes.
Conclusions: We have developed a novel method for the detection of the TLR4 Asp299Gly and Thr399Ile mutations, permitting rapid genotyping which should be useful for large-scale population studies as well as applicable for routine clinical testing.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jim.2004.03.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study.
Life (Basel)
October 2024
Department of Molecular Sciences, Faculty of Medicine, "Iuliu Hațieganu" University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania.
Article Synopsis
- * The study examined the relationship between certain gene variations (polymorphisms) of IL17 and TLR4 and their impact on the likelihood of developing metabolic associated fatty liver disease (MASLD), using genetic testing and serum level analysis.
- * Findings revealed that individuals with specific genetic variants of IL17 and TLR4 had significantly higher odds of developing conditions like metabolic associated steatotic liver disease (MASH) and metabolic associated fatty liver (MAFL); notably, certain alleles were strongly correlated with these increased risks.
TLR4 and TNF-α single nucleotide polymorphisms in patients with brucellosis: Association with infection complications.
Eur J Intern Med
January 2025
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Centre of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece.
Objectives: To investigate associations of the carriage of single nucleotide polymorphisms (SNPs) of proteins involved in the immune response of patients with brucellosis.
Methods: A case control study of patients with brucellosis upon WHO criteria. Blood genomic analysis was performed by RFLP- PCR for the detection of SNPs: i) at promoters -376 G > A (rs1800750); -308 G > A (rs 1,800,629); -238 G > A (rs361525) of the TNF gene, ii) at -896 A > G Asp299Gly (rs4986790) and -1196 C > T Thr399Ile (rs4986791) positions of the TLR-4 gene.
Association of TLR4 polymorphisms (Asp299Gly and Thr399Ile) with sepsis: a meta-analysis and trial sequence analysis.
APMIS
November 2024
Department of Critical care Medicine 330 wards, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Article Synopsis
- The study investigates the genetic variants TLR4 Asp299Gly and Thr399Ile in relation to sepsis, highlighting contradictory findings from previous research.
- A meta-analysis was performed on 13 studies involving over 4,800 participants, suggesting that the Asp299Gly variant might offer a slight protective effect against sepsis, although results were not statistically significant.
- The authors stress the need for more extensive research with larger and more varied populations to confirm these potential associations and clarify the role of TLR4 polymorphisms in sepsis.
Genotype Frequency of the Common TLR4 SNPs in a Kurdish Population: Global Reviews and Out-of-African Migrations.
Hum Biol
September 2023
Department of Biology, College of Education, University of Garmian, Kalar, Kurdistan Region, Iraq.
Toll-like receptors (TLRs) are cellular innate immune receptors that explore microbial molecules. For instance, TLR4 can sense bacterial lipopolysaccharides, inducing cytokines and antimicrobial peptides against the bacteria. Single-nucleotide polymorphisms (SNPs) in TLR4 are associated with diseases such as septic shock.
View Article and Find Full Text PDFFrequency of toll-like receptor 4 variants and association with treatment response in children with primary immune thrombocytopenia.
Pediatr Blood Cancer
November 2023
Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
Objectives: To investigate the frequency of toll-like receptor 4 (TLR4) variants c.896A>G (p.Asp299Gly) and c.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!