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A Polymorphism rs6726395 in Nrf2 Contributes to the Development of Emphysema-Associated Age in Smokers Without COPD

  • A. Sugitani
  • K. AsaiEmail author
  • T. Watanabe
  • T. Suzumura
  • K. Kojima
  • H. Kubo
  • K. Sato
  • N. Ijiri
  • K. Yamada
  • T. Kimura
  • S. Fukumoto
  • K. Hirata
  • T. Kawaguchi



Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood.


Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined.


A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers.


A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.


Emphysema COPD Single nucleotide polymorphism NF-E2-related factor2 Percentage of low-attenuation area 



Genotyping analyses were performed in the Research Support Platform of Osaka City University Graduate School of Medicine.

Compliance with Ethical Standards

Conflict of interest

The authors have stated explicitly that there is no conflict of interest in connection with this article.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Respiratory Medicine, Graduate School of MedicineOsaka City UniversityOsakaJapan
  2. 2.Department of Premier Preventive Medicine, Graduate School of MedicineOsaka City UniversityOsakaJapan

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