ATF6B 多态性可能与哮喘患者阿司匹林激发后 FEV1 下降有关。
Polymorphisms of ATF6B Are Potentially Associated With FEV1 Decline by Aspirin Provocation in Asthmatics.
机构信息
Department of Life Science, Sogang University, Seoul, Korea.
Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea.
出版信息
Allergy Asthma Immunol Res. 2014 Mar;6(2):142-8. doi: 10.4168/aair.2014.6.2.142. Epub 2013 Nov 28.
PURPOSE
Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6β (ATF6B) is known to regulate ATFα-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation.
METHODS
Four common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) as controls.
RESULTS
Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected P=0.02) were significantly associated with % decline of FEV1 by aspirin provocation, whereas ATF6B polymorphisms and haplotypes were not associated with the risk of AERD.
CONCLUSIONS
Although further functional and replication studies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure in adult asthmatics.
目的
内质网（ER）应激最近被观察到能激活 NF-κB 并诱导哮喘等炎症反应。激活转录因子 6β（ATF6β）已知能调节 ATFα 介导的 ER 应激反应。本研究旨在探讨 ATF6β 基因变异与阿司匹林加重的呼吸道疾病（AERD）及其主要表型，即阿司匹林激发后 FEV1 下降的%之间的关联。
方法
对 93 例 AERD 患者和 96 例阿司匹林耐受哮喘（ATA）对照者的 ATF6B 中的 4 个常见单核苷酸多态性（SNP）进行基因分型和统计学分析。
结果
logistic 分析显示，2 个 SNP（rs2228628 和 rs8111，P=0.008；校正 P=0.03）和 1 个单倍型（ATF6B-ht4，P=0.005；校正 P=0.02）与阿司匹林激发后 FEV1 下降的%显著相关，而 ATF6B 多态性和单倍型与 AERD 的风险无关。
结论
尽管需要进一步的功能和复制研究，但我们的初步发现表明，ATF6β 可能与成年哮喘患者对阿司匹林暴露的反应中阻塞表型有关。
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