Toll-Like receptor 4 (TLR4) polymorphism rs2149356 and risk of gout in a Spanish cohort

Nucleosides Nucleotides Nucleic Acids. 2020;39(10-12):1424-1431. doi: 10.1080/15257770.2020.1780438. Epub 2020 Jun 18.

Abstract

Gout is the most common arthritis and it is associated to urate monosodium crystals deposits in articulations, kidney and soft tissue. The urate monosodium crystals deposit initiates an inflammatory response; mediated by NLRP3 inflammasome, with the release of interleukin 1β. Toll-like receptor 4 (TLR4) is involved in this response. Although serum urate level is a strong predictor of incident gout, only about half of those with serum urate concentrations ≥10mg/dL develop clinically evident gout over 15 years. Therefore, it has been postulated that other factors, including genetic or immunity related factors, seems to be necessary to the apparition of the acute gout flare beside hyperuricemia. The association of TLR4 single nucleotide polymorphism (SNP) rs2149356 and gout risk is controversial with different results according to different populations.Methods: We have analyzed rs2149356 polymorphism of TLR4 gene in DNA extracted from 125 well characterized Caucasian gouty patients and 300 Caucasian health controls, by automated DNA sequencing.Results: Allele frequency distribution in control samples were CC: 0.467 (140); CA 0.437 (131); and AA 0.097 (29).Allele distribution in gouty patients were CC: 0.512 (64); CA: 0.392 (49); and AA: 0.096 (12). No significant association was found between TRL4 rs2149356 polymorphism and risk of gout in the analyzed population.Conclusions: Allele frequency for rs2149356 in our population was similar to other population of European ancestry, and in these populations; the polymorphism was not related to gouty risk.

Keywords: Gout; SNP; TLR4; hyperuricemia.

MeSH terms

  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Gout / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Spain
  • Toll-Like Receptor 4 / genetics*

Substances

  • TLR4 protein, human
  • Toll-Like Receptor 4