Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease.
10.4168/aair.2011.3.2.123
- Author:
Nami Shrestha PALIKHE
1
;
Seung Hyun KIM
;
Joo Hee KIM
;
Purevsuren LOSOL
;
Young Min YE
;
Hae Sim PARK
Author Information
1. Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, Korea. hspark@ajou.ac.kr
- Publication Type:Original Article
- Keywords:
TLR3 polymorphism;
aspirin sensitivity;
asthma;
viral infection
- MeSH:
Alleles;
Asthma;
Gene Frequency;
Genotype;
Haplotypes;
Humans;
Inflammation;
Interferon-gamma;
Korea;
Phenotype;
Polymorphism, Genetic;
RNA, Double-Stranded;
Toll-Like Receptor 3;
Toll-Like Receptors;
Viral Structures
- From:Allergy, Asthma & Immunology Research
2011;3(2):123-127
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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-kappaB and increases interferon-gamma, 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.
