Higher Levels of Serum TLR2 and TLR4 in Patients with Hashimoto's Thyroiditis

Endocr Metab Immune Disord Drug Targets. 2020;20(1):118-126. doi: 10.2174/1871530319666190329114621.

Abstract

Objective: Hashimoto's thyroiditis (HT) is an autoimmune disorder caused by the interaction between genes and environmental triggers. HT is the most common endocrine disorder, as well as the most common cause of hypothyroidism. Autoimmunity plays a crucial role in the pathogenesis of HT and recent studies suggest that Toll-like receptor (TLR) signals lead to increased inflammatory response. The aim of our study is to investigate whether TLR-2 and TLR-4 levels and gene polymorphisms contribute to the damaged immune response leading to HT.

Methods: Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, single-nucleotide polymorphisms (SNPs) of TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile were studied in 100 patients with HT and 100 healthy controls. Also, we investigated serum levels of TLR-2 and TLR-4 in the immunopathogenesis of HT. TLR-2 and TLR-4 serum levels were found to be significantly higher in HT patients than the control group. However, no statistical significance was found between patient and control groups in terms of genotype frequencies and allele frequency distribution of TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile polymorphisms.

Result: TLR2 gene Arg677Trp, Arg753Gln, 196-174 del and TLR4 gene Asp299Gly, Thr399Ile polymorphism do not appear to have a role in the development of HT disease. However, in our study, serum levels of TLR-2 and TLR-4 were found to be higher in HT patients than control groups.

Conclusion: These findings suggest that TLR-2 and TLR-4 play an important role in the immunopathologic mechanism of disease by causing an increase in proinflammatory response.

Keywords: Arg677Trp; Arg753Gln; Asp299Gly; Hashimoto’s thyroiditis; TLR2; TLR4; polymorphism..

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Hashimoto Disease / blood*
  • Hashimoto Disease / diagnosis
  • Hashimoto Disease / genetics
  • Hashimoto Disease / immunology
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Toll-Like Receptor 2 / blood*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 4 / blood*
  • Toll-Like Receptor 4 / genetics
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4