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 associationsof 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 patientsand 96 aspirin-tolerant asthma (ATA) as controls. Results: Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; correctedP=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 replicationstudies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure inadult asthmatics.