Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung

Aoi Kuroda, Ahmed E. Hegab, Gao Jingtao, Shuji Yamashita, Nobuyuki Hizawa, Tohru Sakamoto, Hideyasu Yamada, Satoshi Suzuki, Makoto Ishii, Ho Namkoong, Takanori Asakura, Mari Ozaki, Hiroyuki Yasuda, Junko Hamamoto, Shizuko Kagawa, Kenzo Soejima, Tomoko Betsuyaku

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. Methods: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice. Results: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice. Conclusions:ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect.

Original languageEnglish
Article number69
JournalRespiratory Research
Volume18
Issue number1
DOIs
Publication statusPublished - 2017 Apr 21

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Aldehyde Dehydrogenase
Lung
Genes
Stem Cells
Transgenic Mice
Alleles
Chronic Obstructive Pulmonary Disease
Mitochondria
Asthma
Epithelial Cells
Premature Aging
Acute Lung Injury
Emphysema
Lung Injury
Trachea
Aldehydes
Smoke
Tobacco Products
Human Influenza
Population

Keywords

  • Aldehyde
  • ALDH2
  • Basal cell
  • Club cell
  • Epithelial cell
  • Lung
  • Mitochondria
  • Stem cell
  • Trachea

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Kuroda, A., Hegab, A. E., Jingtao, G., Yamashita, S., Hizawa, N., Sakamoto, T., ... Betsuyaku, T. (2017). Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung. Respiratory Research, 18(1), [69]. https://doi.org/10.1186/s12931-017-0554-5

Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung. / Kuroda, Aoi; Hegab, Ahmed E.; Jingtao, Gao; Yamashita, Shuji; Hizawa, Nobuyuki; Sakamoto, Tohru; Yamada, Hideyasu; Suzuki, Satoshi; Ishii, Makoto; Namkoong, Ho; Asakura, Takanori; Ozaki, Mari; Yasuda, Hiroyuki; Hamamoto, Junko; Kagawa, Shizuko; Soejima, Kenzo; Betsuyaku, Tomoko.

In: Respiratory Research, Vol. 18, No. 1, 69, 21.04.2017.

Research output: Contribution to journalArticle

Kuroda, A, Hegab, AE, Jingtao, G, Yamashita, S, Hizawa, N, Sakamoto, T, Yamada, H, Suzuki, S, Ishii, M, Namkoong, H, Asakura, T, Ozaki, M, Yasuda, H, Hamamoto, J, Kagawa, S, Soejima, K & Betsuyaku, T 2017, 'Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung', Respiratory Research, vol. 18, no. 1, 69. https://doi.org/10.1186/s12931-017-0554-5
Kuroda, Aoi ; Hegab, Ahmed E. ; Jingtao, Gao ; Yamashita, Shuji ; Hizawa, Nobuyuki ; Sakamoto, Tohru ; Yamada, Hideyasu ; Suzuki, Satoshi ; Ishii, Makoto ; Namkoong, Ho ; Asakura, Takanori ; Ozaki, Mari ; Yasuda, Hiroyuki ; Hamamoto, Junko ; Kagawa, Shizuko ; Soejima, Kenzo ; Betsuyaku, Tomoko. / Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung. In: Respiratory Research. 2017 ; Vol. 18, No. 1.
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AU - Kuroda, Aoi

AU - Hegab, Ahmed E.

AU - Jingtao, Gao

AU - Yamashita, Shuji

AU - Hizawa, Nobuyuki

AU - Sakamoto, Tohru

AU - Yamada, Hideyasu

AU - Suzuki, Satoshi

AU - Ishii, Makoto

AU - Namkoong, Ho

AU - Asakura, Takanori

AU - Ozaki, Mari

AU - Yasuda, Hiroyuki

AU - Hamamoto, Junko

AU - Kagawa, Shizuko

AU - Soejima, Kenzo

AU - Betsuyaku, Tomoko

PY - 2017/4/21

Y1 - 2017/4/21

N2 - Background: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. Methods: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice. Results: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice. Conclusions:ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect.

AB - Background: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer's diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. Methods: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 -/- mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 -/- mice. Results: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 -/- and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 -/- mice. Aldh2 -/- tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 -/- mice than in WT mice. Conclusions:ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a "premature lung aging" effect.

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KW - ALDH2

KW - Basal cell

KW - Club cell

KW - Epithelial cell

KW - Lung

KW - Mitochondria

KW - Stem cell

KW - Trachea

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