Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics
Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics
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DOI：
10.1097/fpc.0b013e328361d4bb
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发表时间：
2013-07-01
影响因子：
2.6
通讯作者：
Park, Choon-Sik
中科院分区：
文献类型：
--
作者：
Cho, Sung-hwan;Park, Jong-Sook;Park, Choon-Sik
研究背景阿司匹林加重的呼吸道疾病（AERD）是哮喘患者在服用阿司匹林或其他非甾体抗炎药后发生的气道阻塞。TAPBP（TAP结合蛋白，tapasin）被类花生酸上调，类花生酸在阿司匹林相关反应中充当强效炎症分子。因此，在TAPBP基因的功能改变可能有助于对AERD.ObjectivesWe研究的TAPBP基因和AERD.Materials和methodsA组哮喘患者（n=1252）的单核苷酸多态性之间的关系进行了口服阿司匹林的挑战。口服阿司匹林激发反应分为以下两组：1 s内用力呼气量减少15%或以上或鼻眼和皮肤反应（AERD），或1 s内用力呼气量减少15%或以下而无鼻眼和皮肤反应（阿司匹林耐受性哮喘）。结果Logistic回归分析显示，TAPBP基因rs 2071888 C>G的等位基因频率与TAPBP基因多态性的频率呈负相关（P <0.05），与TAPBP基因多态性的频率呈负相关（P <0.05）。（Thr 260 Arg）外显子4与rs 10592883 UTR上的T>C基因绝对连锁不平衡的等位基因频率在AERD组显著高于阿司匹林耐受性哮喘组（P>0.05），经多重比较，P值仍有显著性意义（P-corr=0.006，OR：1.37，95%可信区间：1.11-1.69，加性模型; P-corr=0.009，OR：1.52，95%可信区间：1.14-2.03，显性模型）。结论TAPBP基因多态性可能与AERD的发生有关。
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>G (Thr260Arg) on exon 4 (P>0.05), which was in absolute linkage disequilibrium with rs1059288 T>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.