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Title: Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics. Author: Cho SH, Park JS, Park BL, Bae DJ, Uh ST, Kim MK, Choi IS, Shin HD, Park CS. Journal: Pharmacogenet Genomics; 2013 Jul; 23(7):341-8. PubMed ID: 23736108. Abstract: BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by the development of airway obstruction in asthmatic individuals following the ingestion of aspirin or other nonsteroidal anti-inflammatory drugs. TAPBP (TAP-binding protein, tapasin) is upregulated by eicosanoids, which act as potent inflammatory molecules in aspirin-related reactions. Thus, functional alterations in the TAPBP gene may contribute toward AERD. OBJECTIVES: We examined the relationship between the single nucleotide polymorphisms on the TAPBP gene and AERD. MATERIALS AND METHODS: A group of asthmatic patients (n=1252) underwent the oral aspirin challenge. Oral aspirin challenge reactions were categorized into two groups as follows: 15% or greater decreases in forced expiratory volume in 1 s or naso-ocular and skin reactions (AERD), or 15% or less decreases in forced expiratory volume in 1 s without naso-ocular and skin reactions (aspirin-tolerant asthma). Five single nucleotide polymorphisms of the TAPBP gene were genotyped. RESULTS: Logistic regression analysis showed that the minor allele frequencies of TAPBP rs2071888 C>G (Thr260Arg) on exon 4 (P>0.05), which was in absolute linkage disequilibrium with rs1059288 T>C on 3'UTR, were significantly higher in the AERD group than in the aspirin-tolerant asthma group, and the P values remained significant after multiple comparisons (Pcorr=0.006, odds ratio: 1.37, 95% confidence interval: 1.11-1.69, additive model; Pcorr=0.009, odds ratio: 1.52, 95% confidence interval: 1.14-2.03, dominant model). Alpha-helical wheel plotting showed that 260Arg had greater hydrophilic helical property than 260Thr. CONCLUSION: TAPBP polymorphisms may play a role in the development of AERD.[Abstract] [Full Text] [Related] [New Search]