Journals / Dicle Tıp Dergisi / 2026 / Cilt: 46 Sayı: 2

Investigation of the Asp299Gly and Thr399Ile polymorphisms of TLR4 gene in Rheumatoid Arthritis

Pages
255–268
Publication Date
2019-06-11
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Results and Conclusion: According to the results obtained from RA patients and healthy controls, we have not found any statistical difference between both groups.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Objective: Rheumatoid arthritis (RA) is a chronic and inflammatory disease characterized by synovial inflammation that causes cartilage and bone destruction as well as systemic defects, including cardiovascular, pulmonary, psychological, and skeletal disorders.
📊
Key Findings & Data:Toll-like receptors (TLRs) are transmembrane glycoproteins that are related to inflammation via synthesis of proinflammatory cytokines like TNF-α, IL-6, and IL-1β.
💡
Conclusion & Impact:Results and Conclusion: According to the results obtained from RA patients and healthy controls, we have not found any statistical difference between both groups.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Rheumatoid Arthritis · Toll-like receptor 4 · polymorphism

Özet

Objective: Rheumatoid arthritis (RA) is a chronic and inflammatory disease characterized by synovial inflammation that causes cartilage and bone destruction as well as systemic defects, including cardiovascular, pulmonary, psychological, and skeletal disorders. The etiology of RA is unclear. Evidence suggests that RA is influenced by both genetic and environmental factors and the inflammatory and autoimmune activities take important roles in the development of this disease. In the onset of RA, an interaction between the resident cells of synovium and cells of the innate and adaptive immune system reported. Fibroblast-like synoviocytes (FLS) are one of the resident cells and they play a central role, with a tumor-like behavior, in joint destruction and development of chronic inflammation. Toll-like receptors (TLRs) are transmembrane glycoproteins that are related to inflammation via synthesis of proinflammatory cytokines like TNF-α, IL-6, and IL-1β. Some studies report an association between the activation of FLS and the cytokine environment, cell-to-cell contacts, or the activation of TLR2, TLR4, and TLR3. TLRs and especially TLR4 is involved in the recognition of endogenous molecules released by injured tissues and necrotic cells. TLR4 gene involved in a wide variety of both infectious and non-infectious diseases and two polymorphisms of TLR4, Asp299Gly and Thr399Ile, changed the binding capacity and electrical charge of the protein. There are conflicting or even contradictory results about these polymorphisms and we aimed to determine the distribution of the allele frequencies of these polymorphisms and compare the result of RA patients with healthy subjects. Methods: DNA extraction was realized by salting out method from peripheral blood lymphocytes of RA patients and healthy controls. PCR amplification carried out with appropriate primer pairs against the related DNA sequences. Genotyping performed by the restriction fragment length polymorphism method. Results and Conclusion: According to the results obtained from RA patients and healthy controls, we have not found any statistical difference between both groups. Including the other polymorphisms of the TLR family into this type of studies, will give more information about the role of TLR family in rheumatoid arthritis.

🔖

Cite This Article

Yildirim, İ. H., Uzen, R. (2019). Investigation of the Asp299Gly and Thr399Ile polymorphisms of TLR4 gene in Rheumatoid Arthritis. Dicle Tıp Dergisi, Cilt: 46 Sayı: 2, 255–268. https://doi.org/10.5798/dicletip.540004

References (18)

  1. Spector TD. Rheumatoid arthritis. Rheum Dis Clin North Am 1990; 16: 513–37.
  2. McInnes IB, Schett G. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med 2011; 365: 2205-19.
  3. Choy EHS, Panayi GS. Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis. N Engl J Med 2011; 344: 907-16.
  4. Yarwood A, Huizinga TWJ, Worthington J. The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA. Rheumatology (Oxford). 2016; 55:199–209.
  5. Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010; 233: 233-55.
  6. Hu F, Li Y, Shi L, et all. (2014) Toll-Like Receptors Expressed by Synovial Fibroblasts Perpetuate Th1 and Th17 Cell Responses in Rheumatoid Arthritis. PLoS ONE 9(6): e100266. doi:10.1371/journal.pone.0100266
  7. Molteni M, Gemma S, Rossetti C. The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation. Mediators of Inflammation Volume 2016, Article ID 6978936, 9 pages
  8. Zhang B, Ramesh G, Uematsu S, Akira S, Reeves WR. TLR signaling mediates inflammation and tissue injury in nephrotoxicity. J Am Soc Nephrol 2008; 19: 923–32.
  9. Sabroe I, Parker LC, Dower SK, Whyte MKB, The role of TLR activation in inflammation. J Pathol 2008; 214: 126-135.
  10. Kutikhin AG. Impact of Toll-like receptor 4 polymorphisms on risk of cancer. Human Immunology 2011: 193-206.
  11. Lorenz E, Frees KL, Schwartz DA. Determination of the TLR4 genotype using allele-specific PCR. Biotechniques 2001; 31: 22-4.
  12. Stebulis JA, Rossetti RG, Atez FJ, Zurier RB. Fibroblast-like synovial cells derived from synovial fluid. J Rheumatol 2005; 32: 301-6.
  13. Gülen F, Köksoy H, Tanaç R, et all. Astım ve alerjik Rinitli Çocuklarda Toll Like Reseptör 2 ve Toll Like Resptör 4 Polimorfizmi. The Journal of Pediatric Research 20014; 1: 13-21.
  14. Jung YO, Cho ML, Kang CM, et all. Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts. Immunol Lett 2007; 109: 21–27.
  15. Kagan JC, Su T, Horng T, et all. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat Immunol. 2008; 9: 361-8.
  16. Trejo-de la OA, Torres J, PÊrez-RodrIguez M, et all. TLR4 single-nucleotide polymorphisms alter mucosal cytokine and chemokine patterns in Mexican patients with Helicobacter pylori-associated gastroduodenal diseases. Clin Immunol 2008; 129: 333–40.
  17. Arbour NC, Lorenz E, Schutte BC, et all. TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000; 5: 187-91.
  18. Barber RC, Chang LY, Arnoldo BD, et all. Innate immunity SNPs are associated with risk for severe sepsis after burn injury. Clin Med Res. 2006; 4: 250-5.