Polymorphisms of ATF6B Are Potentially Associated With FEV1 Decline by Aspirin Provocation in Asthmatics

Abstract

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.

Keywords: ATF6B; aspirin exacerbated respiratory disease (AERD); haplotype; single nucleotide polymorphism (SNP).

Figure

Physical map, haplotypes and LD of ATF6B. (A) Polymorphisms of ATF6B investigated in this study. Coding exons are marked by black blocks; 5'- and 3'-untranslated region (UTR) by white blocks. (B) Haplotypes of ATF6B in the Korean asthmatics. (C) LD blocks among ATF6B polymorphisms.