title: Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease.
abstract: OBJECTIVE
  Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-κB and increases interferon-γ, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD.
  
  
  METHODS
  The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods.
  
  
  RESULTS
  Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models.
  
  
  CONCLUSIONS
  Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.
authors: Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, Korea.
authors: Nami Shrestha
authors: NS
authors: Palikhe
authors: Seung-Hyun
authors: SH
authors: Kim
authors: Joo-Hee
authors: JH
authors: Kim
authors: Purevsuren
authors: P
authors: Losol
authors: Young-Min
authors: YM
authors: Ye
authors: Hae-Sim
authors: HS
authors: Park