Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics

作者：Cho Sung hwan; Park Jong Sook; Park Byung Lae; Bae Da Jeong; Uh Soo Taek; Kim Mi Kyeong; Choi Inseon S; Shin Hyoung Doo; Park Choon Sik^*

来源：Pharmacogenetics and Genomics, 2013, 23(7): 341-348.

DOI：10.1097/FPC.0b013e328361d4bb

• aspirin-exacerbated respiratory disease
• aspirin-tolerance asthma
• single nucleotide polymorphism
• TAP-binding protein

BackgroundAspirin-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.ObjectivesWe examined the relationship between the single nucleotide polymorphisms on the TAPBP gene and AERD.Materials and methodsA 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.ResultsLogistic regression analysis showed that the minor allele frequencies of TAPBP rs2071888 C%26gt;G (Thr260Arg) on exon 4 (P%26gt;0.05), which was in absolute linkage disequilibrium with rs1059288 T%26gt;C on 3UTR, were significantly higher in the AERD group than in the aspirin-tolerant asthma group, and the P values remained significant after multiple comparisons (P-corr=0.006, odds ratio: 1.37, 95% confidence interval: 1.11-1.69, additive model; P-corr=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.ConclusionTAPBP polymorphisms may play a role in the development of AERD.

• 出版日期2013-7
• 单位河北医科大学