Allergy Asthma Immunol Res.  2014 Mar;6(2):142-148. 10.4168/aair.2014.6.2.142.

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

• Park TJ
• Kim JH
• Pasaje CF
• Park BL
• Bae JS
• Uh ST
• Kim YH
• Kim MK
• Choi IS
• Choi BW
• Shin HR
• Park JS
• Koh I
• Park CS
• Shin HD

• KMID: 2260259
• DOI: http://doi.org/10.4168/aair.2014.6.2.142

Abstract

PURPOSE
Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6beta (ATF6B) is known to regulate ATFalpha-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.

Keyword

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

MeSH Terms

Adult
Aspirin*
Asthma
Endoplasmic Reticulum
Haplotypes
Humans
Methods
NF-kappa B
Phenotype
Polymorphism, Single Nucleotide
Transcription Factors
Aspirin
NF-kappa B
Transcription Factors

Figure

• 

  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.

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