Association between the aldehyde dehydrogenase 2*2 allele and smoking-related chronic airway obstruction in a Japanese general population: A pilot study

Morita, Kazunori; Masuda, Natsuki; Oniki, Kentaro; Saruwatari, Junji; Kajiwara, Ayami; Otake, Koji; Ogata, Yasuhiro; Nakagawa, Kazuko

doi:10.1016/j.toxlet.2015.05.007

Cited by 5 publications

(4 citation statements)

References 29 publications

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“… 10 In the previous reports, the ALDH2*2 allele, in combination with a mild elevation in the GGT level, drinking habit and/or smoking habit, was associated with an increased risk for hypertension, 18 diabetic retinopathy, 13 myocardial infarction 19 or chronic airway obstruction. 15 According to these findings, ALDH2 may therefore have a critical role in the protection against toxic aldehydes generated under sustained high oxidative stress conditions, and our findings thus suggest that the GGT level should be carefully monitored for the prevalence of NAFLD, especially in ALDH2*2 allele carriers.…”

Section: Discussionsupporting

confidence: 55%

“…In this model, the odds ratios and 95% confidence intervals (CIs) were measured according to the generalized estimating equations approach as we reported previously. 15 The fitness of the multivariable logistic regression models was determined using the quasi-likelihood criterion. According to the final logistic regression models, the C-statistics, that is, area under the curve values, with 95% CI of the ROC curve were also calculated using the logit function of the individual probability values for the prevalence of NAFLD.…”

Section: Methodsmentioning

confidence: 99%

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The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease

et al. 2016

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Aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes and has a key role in protecting the liver. An elevated gamma-glutamyl transferase (GGT) level is related to oxidative stress and nonalcoholic fatty liver disease (NAFLD). We herein investigated the association between inactive ALDH2*2 allele (rs671) and the risk of NAFLD, including the relationship to the GGT level. A retrospective follow-up study (mean 5.4±1.1 years) was conducted among 341 Japanese health screening program participants. The receiver operating characteristic curve indicated that the GGT level predicted the development of NAFLD (area under the curve: 0.65, P<0.05) with a cutoff value of 25.5 IUl−1. The longitudinal risk of NAFLD was higher in the ALDH2*2 allele carriers than in the noncarriers (odds ratio (OR): 2.30, 95% confidence interval (CI): 1.21–4.40), and the risk was further increased among the *2 allele carriers with GGT values ⩾25.5 IUl−1 (OR: 4.28, 95% CI: 1.80–10.19). On the other hand, there were no significant changes in the subjects' body weight and body mass index during observation period. The ALDH2*2 allele, in relation to the GGT level, may potentially be a novel risk factor for NAFLD.

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Section: Discussionsupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease

et al. 2016

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“…Overall, in contrast to our hypothesis, we found no profound impact of aldehydes on molecular mechanisms controlling mitochondrial content and function, compared with CS. This is in contrast to in vitro studies which showed that acrolein or co-exposure to acrolein and formaldehyde disrupts processes involved in the regulation of mitochondrial homeostasis in lung cells [ 70 , 79 , 95 , 98 , 103 ], and conflicts with an in vivo study which observed that proper function of aldehyde dehydrogenase protected against the development of CS-induced airway disease [ 48 ]. Probably, the use of our sophisticated and novel exposure model, giving consideration to the above-mentioned corresponding limitations, e.g., dosimetry, could clarify the limited impact of aldehydes on the molecular regulation of pathways involved in mitochondrial content and function.…”

Section: Discussionmentioning

confidence: 58%

“…The exact chemical constituents of CS responsible for these mitochondrial abnormalities are unknown. Interestingly, Morita et al previously showed an association between the presence of an inactive allele of aldehyde dehydrogenase (an enzyme that detoxifies aldehydes) and increased incidence of smoking-related chronic airway obstruction in a Japanese population [ 48 ]. Moreover, it has been shown that in vivo acrolein exposure resulted in impaired lung function and structure [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Smoking-Associated Exposure of Human Primary Bronchial Epithelial Cells to Aldehydes: Impact on Molecular Mechanisms Controlling Mitochondrial Content and Function

Duistermaat

Cremers

Klerx

et al. 2022

Cells

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Chronic obstructive pulmonary disease (COPD) is a devastating lung disease primarily caused by exposure to cigarette smoke (CS). During the pyrolysis and combustion of tobacco, reactive aldehydes such as acetaldehyde, acrolein, and formaldehyde are formed, which are known to be involved in respiratory toxicity. Although CS-induced mitochondrial dysfunction has been implicated in the pathophysiology of COPD, the role of aldehydes therein is incompletely understood. To investigate this, we used a physiologically relevant in vitro exposure model of differentiated human primary bronchial epithelial cells (PBEC) exposed to CS (one cigarette) or a mixture of acetaldehyde, acrolein, and formaldehyde (at relevant concentrations of one cigarette) or air, in a continuous flow system using a puff-like exposure protocol. Exposure of PBEC to CS resulted in elevated IL-8 cytokine and mRNA levels, increased abundance of constituents associated with autophagy, decreased protein levels of molecules associated with the mitophagy machinery, and alterations in the abundance of regulators of mitochondrial biogenesis. Furthermore, decreased transcript levels of basal epithelial cell marker KRT5 were reported after CS exposure. Only parts of these changes were replicated in PBEC upon exposure to a combination of acetaldehyde, acrolein, and formaldehyde. More specifically, aldehydes decreased MAP1LC3A mRNA (autophagy) and BNIP3 protein (mitophagy) and increased ESRRA protein (mitochondrial biogenesis). These data suggest that other compounds in addition to aldehydes in CS contribute to CS-induced dysregulation of constituents controlling mitochondrial content and function in airway epithelial cells.

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Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung

et al. 2022

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Association between the aldehyde dehydrogenase 2*2 allele and smoking-related chronic airway obstruction in a Japanese general population: A pilot study

Cited by 5 publications

References 29 publications

The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease

The longitudinal effect of the aldehyde dehydrogenase 2*2 allele on the risk for nonalcoholic fatty liver disease

Smoking-Associated Exposure of Human Primary Bronchial Epithelial Cells to Aldehydes: Impact on Molecular Mechanisms Controlling Mitochondrial Content and Function

Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung

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