ArticleProceedings of the National Academy of Sciences of the United States of America2015
ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 94 citations in OpenAlex.
- Review
- Association of ALDH2 rs671 Polymorphism with chronic kidney disease incidence in a population-based Korean cohort.Scientific reports · 2026Article
- Unravelling the molecular mechanisms causal to type 2 diabetes across global populations and disease-relevant tissues.Nature metabolism · 2026Article
- ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury.Circulation · 2026Article
- Etiology-Driven Mouse Models of Hepatocellular Carcinoma: Paving the Way for Precision Oncology.Journal of hepatocellular carcinoma · 2026Review
- Trend of liver cancer attributable to alcohol use in China from 1992 to 2021: An age-period-cohort analysis study.PloS one · 2026Article
- Aldehyde Dehydrogenase 2 Gene Polymorphism and Alcohol Consumption Are Associated With Nephrolithiasis in a Chinese Population.Molecular genetics & genomic medicine · 2026Article
- Targeted Overexpression of Mitochondrial ALDH2 in Coronary Endothelial Cells Mitigates HFpEF in a Diabetic Mouse Model.Biomolecules · 2025Article
- The aldehyde dehydrogenase 2 rs671 variant enhances amyloid β pathology.Nature communications · 2024Article
- ALDH2 is a novel biomarker and exerts an inhibitory effect on melanoma.Scientific reports · 2024Article
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- Identifying the Molecular Drivers of Pathogenic Aldehyde Dehydrogenase Missense Mutations in Cancer and Non-Cancer Diseases.International journal of molecular sciences · 2023Article
- Alcohol as a Modifiable Risk Factor for Alzheimer's Disease-Evidence from Experimental Studies.International journal of molecular sciences · 2023Review
- Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease.Journal of translational medicine · 2023Review
- Patients with Non-Alcoholic Fatty Liver Disease and Alcohol Dehydrogenase 1B/Aldehyde Dehydrogenase 2 Mutant Gene Have Higher Values of Serum Alanine Transaminase.Journal of personalized medicine · 2023Article
- Gene Therapy to Treat Osteopenia Associated With Chronic Ethanol Consumption and Aldehyde Dehydrogenase 2 Deficiency.JBMR plus · 2023Article
- Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets.MedComm · 2023Review
- SGLT2 inhibitor ameliorates endothelial dysfunction associated with the commonScience translational medicine · 2023Article
- Review
- Alcoholic liver disease: a new insight into the pathogenesis of liver disease.Archives of pharmacal research · 2022Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the liver removes toxic aldehydes including acetaldehyde, an intermediate of ethanol metabolism. Nearly 40% of East Asians inherit an inactive ALDH2*2 variant, which has a lysine-for-glutamate substitution at position 487 (E487K), and show a characteristic alcohol flush reaction after drinking and a higher risk for gastrointestinal cancers. Here we report the characterization of knockin mice in which the ALDH2(E487K) mutation is inserted into the endogenous murine Aldh2 locus. These mutants recapitulate essentially all human phenotypes including impaired clearance of acetaldehyde, increased sensitivity to acute or chronic alcohol-induced toxicity, and reduced ALDH2 expression due to a dominant-negative effect of the mutation. When treated with a chemical carcinogen, these mutants exhibit increased DNA damage response in hepatocytes, pronounced liver injury, and accelerated development of hepatocellular carcinoma (HCC). Importantly, ALDH2 protein levels are also significantly lower in patient HCC than in peritumor or normal liver tissues. Our results reveal that ALDH2 functions as a tumor suppressor by maintaining genomic stability in the liver, and the common human ALDH2 variant would present a significant risk factor for hepatocarcinogenesis. Our study suggests that the ALDH2*2 allele-alcohol interaction may be an even greater human public health hazard than previously appreciated.
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