Association of Genetic Variants of Oxidative Stress Responsive Kinase 1 (OXSR1) with Asthma Exacerbations in Non-Smoking Asthmatics

Abstract

Background: Asthma exacerbation threatens patient's life. Several genetic studies have been conducted to determine the risk factors for asthma exacerbation, but this information is still lacking. We aimed to determine whether genetic variants of Oxidative Stress Responsive Kinase 1(OXSR1), a gene with functions of salt transport, immune response, and oxidative stress, are associated with exacerbation of asthma.Methods: Clinical data were obtained from 1,454 asthmatics and single nucleotide polymorphisms (SNPs) of OXSR1 were genotyped. Genetic associations with annual exacerbation rate were analyzed depending on smoking status. Results: Eleven SNPs were selected using Asian data in the International HapMap database. The common allele of rs1384006 C>T of OXSR1 showed a significantly higher annual exacerbation rate than the rare allele in non-smoking asthmatics (CC vs. CT vs. TT: 0.43 ± 0.04 vs. 0.28 ± 0.03 vs. 0.31 ± 0.09, P=0.004, Pcorr=0.039). The frequent exacerbators had a significantly higher frequency of the common allele of rs1384006 C>T than did the infrequent exacerbators (74.4% vs. 55.2%, P=0.004, P corr=0.038). Conclusion: The common allele of rs1384006 C>T of OXSR1 was associated with the asthma exacerbation rate and a higher risk of being a frequent exacerbator, indicating that non-smoking asthmatics who carry common alleles may be vulnerable to asthma exacerbations.

Asthma Exacerbations: The Genes Behind the Scenes

“…Two recent studies of Korean subjects with asthma revealed genetic associations for AEs in NLRP4 and OXSR1 that differed by smoking status [51,62]. NLRP4 is a regulator of the inflammasome acting as an inhibitor of type I interferon signalling, tumor necrosis factor (TNF)-α and IL-1β-mediated NF-κB activation [69].…”

“…NLRP4 is a regulator of the inflammasome acting as an inhibitor of type I interferon signalling, tumor necrosis factor (TNF)-α and IL-1β-mediated NF-κB activation [69]. Conversely, OXSR1 encodes an oxidative stress responsive kinase that participates in ion transport and cell volume homeostasis [62]. In fact, OXSR1 expression was increased by smoke exposure and glucocorticoid treatment in various airway cell types [62].…”

“…Conversely, OXSR1 encodes an oxidative stress responsive kinase that participates in ion transport and cell volume homeostasis [62]. In fact, OXSR1 expression was increased by smoke exposure and glucocorticoid treatment in various airway cell types [62].…”