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Article: Impact of common ALDH2 inactivating mutation and alcohol consumption on Alzheimer's disease.

Seike, Takuya / Chen, Che-Hong / Mochly-Rosen, Daria

2023 Volume 15, Page(s) 1223977

Abstract: Aldehyde dehydrogenase 2 (ALDH2) is an enzyme found in the mitochondrial matrix that plays a central role in alcohol and aldehyde metabolism. A common ALDH2 polymorphism in East Asians descent (called ALDH2*2 or E504K missense variant, SNP ID: rs671), ... ...

Abstract	Aldehyde dehydrogenase 2 (ALDH2) is an enzyme found in the mitochondrial matrix that plays a central role in alcohol and aldehyde metabolism. A common ALDH2 polymorphism in East Asians descent (called ALDH2*2 or E504K missense variant, SNP ID: rs671), present in approximately 8% of the world's population, has been associated with a variety of diseases. Recent meta-analyses support the relationship between this ALDH2 polymorphism and Alzheimer's disease (AD). And AD-like pathology observed in ALDH2
Language	English
Publishing date	2023-08-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2023.1223977
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: ALDH2 variance in disease and populations.

Chen, Che-Hong / Kraemer, Benjamin R / Mochly-Rosen, Daria

Disease models & mechanisms

2022 Volume 15, Issue 6

Abstract: The ALDH2*2 missense variant that commonly causes alcohol flushing reactions is the single genetic polymorphism associated with the largest number of traits in humans. The dysfunctional ALDH2 variant affects nearly 8% of the world population and is ... ...

Abstract	The ALDH22 missense variant that commonly causes alcohol flushing reactions is the single genetic polymorphism associated with the largest number of traits in humans. The dysfunctional ALDH2 variant affects nearly 8% of the world population and is highly concentrated among East Asians. Carriers of the ALDH22 variant commonly present alterations in a number of blood biomarkers, clinical measurements, biometrics, drug prescriptions, dietary habits and lifestyle behaviors, and they are also more susceptible to aldehyde-associated diseases, such as cancer and cardiovascular disease. However, the interaction between alcohol and ALDH2-related pathology is not clearly delineated. Furthermore, genetic evidence indicates that the ALDH2*2 variant has been favorably selected for in the past 2000-3000 years. It is therefore necessary to consider the disease risk and mechanism associated with ALDH2 deficiency, and to understand the possible beneficial or protective effect conferred by ALDH2 deficiency and whether the pleiotropic effects of ALDH2 variance are all mediated by alcohol use.
MeSH term(s)	Alcohol Drinking/genetics ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; Asian People ; Ethanol ; Humans ; Polymorphism, Genetic
Chemical Substances	Ethanol (3K9958V90M) ; ALDH2 protein, human (EC 1.2.1.3) ; Aldehyde Dehydrogenase, Mitochondrial (EC 1.2.1.3)
Language	English
Publishing date	2022-06-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.049601
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Aldehydes, Aldehyde Metabolism, and the ALDH2 Consortium.

Rwere, Freeborn / Yu, Xuan / Chen, Che-Hong / Gross, Eric R

Biomolecules

2022 Volume 12, Issue 6

Abstract: The discovery of aldehydes dates back to 1774 when Carl Wilhelm Scheele synthesized acetaldehyde [ ... ]. ...

Abstract	The discovery of aldehydes dates back to 1774 when Carl Wilhelm Scheele synthesized acetaldehyde [...].
MeSH term(s)	Acetaldehyde ; Aldehyde Dehydrogenase/genetics ; Aldehyde Dehydrogenase/metabolism ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; Aldehydes/metabolism
Chemical Substances	Aldehydes ; Aldehyde Dehydrogenase (EC 1.2.1.3) ; Aldehyde Dehydrogenase, Mitochondrial (EC 1.2.1.3) ; Acetaldehyde (GO1N1ZPR3B)
Language	English
Publishing date	2022-05-30
Publishing country	Switzerland
Document type	Editorial ; Research Support, N.I.H., Extramural
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12060763
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Article: Implication of the cooking oil-peroxidation product "hydroxynonenal" for Alzheimer's disease.

Yamashima, Tetsumori / Seike, Takuya / Mochly-Rosen, Daria / Chen, Che-Hong / Kikuchi, Mitsuru / Mizukoshi, Eishiro

Frontiers in aging neuroscience

2023 Volume 15, Page(s) 1211141

Abstract: Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that reduces cell injuries via detoxification of lipid-peroxidation product, 4-hydroxy-2-nonenal (hydroxynonenal). It is generated exogenously via deep-frying of linoleic acid-rich cooking oils ... ...

Abstract	Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that reduces cell injuries via detoxification of lipid-peroxidation product, 4-hydroxy-2-nonenal (hydroxynonenal). It is generated exogenously via deep-frying of linoleic acid-rich cooking oils and/or endogenously via oxidation of fatty acids involved in biomembranes. Although its toxicity for human health is widely accepted, the underlying mechanism long remained unknown. In 1998, Yamashima et al. have formulated the "
Language	English
Publishing date	2023-08-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2023.1211141
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Article ; Online: Alcohol Consumption, ALDH2 Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis

Che-Hong Chen / Wen-Lun Wang / Ming-Hung Hsu / Daria Mochly-Rosen

Life, Vol 12, Iss 348, p

2022 Volume 348

Abstract: The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at ... ...

Abstract	The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional ALDH22 missense mutation is a genetic risk factor for UADT cancer. It is not only associated with increased incidences of UADT cancer, but is also implicated in faster cancer progression and poorer prognosis. Alcohol use is a major lifestyle risk factor which causes UADT cancer among ALDH22 carriers. The accumulation of the immediate metabolite of alcohol, acetaldehyde, is likely the genotoxic agents that is involved in the process of tumorigenesis. This review summarizes recent publications on the risk and association of ALDH2*2 mutation, alcohol consumption in synchronous, metachronous UADT cancer. Possible molecular mechanisms involved in cancer initiation, progress and prognosis are discussed. The review also highlights a need for precision medicine-based preventive and therapeutic strategies by integrating lifestyle and genetic risk factors, such as alcohol consumption, genotypes of the alcohol metabolizing genes, ADH1B and ALDH2 , into a risk assessment model for better screening, surveillance and treatment outcome.
Keywords	ALDH2 ; acetaldehyde ; cancer ; upper aerodigestive tract ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comment on: "Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients" by Etienne et al.

Campos, Juliane C / Chen, Che-Hong / Ferreira, Julio C B

Journal of cachexia, sarcopenia and muscle

2020 Volume 11, Issue 6, Page(s) 1858–1859

MeSH term(s)	Aging ; Aldehydes ; Homeostasis ; Humans ; Muscle, Skeletal ; Muscular Dystrophy, Duchenne ; Oxidoreductases
Chemical Substances	Aldehydes ; Oxidoreductases (EC 1.-)
Language	English
Publishing date	2020-07-29
Publishing country	Germany
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.12609
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Alcohol Consumption,

Chen, Che-Hong / Wang, Wen-Lun / Hsu, Ming-Hung / Mochly-Rosen, Daria

Life (Basel, Switzerland)

2022 Volume 12, Issue 3

Abstract	The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional
Language	English
Publishing date	2022-02-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12030348
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Article ; Online: Apolipoprotein E4 allele is genetically associated with risk of the short- and medium-term postoperative cognitive dysfunction: A meta-analysis and trial sequential analysis.

Hsiao, Wei-Jen / Chen, Chien-Yu / Kang, Yi-No / Hu, Chaur-Jong / Chen, Che-Hong / Lin, Pei-Lin / Lin, Yu-Cih

PloS one

2023 Volume 18, Issue 2, Page(s) e0282214

Abstract: The aim of systematic review and meta-analysis was to investigate whether APOE4 was associated with postoperative neurologic dysfunction occurrence in short- or medium-term among surgical patients and to study the potential genetic association among ... ...

Abstract	The aim of systematic review and meta-analysis was to investigate whether APOE4 was associated with postoperative neurologic dysfunction occurrence in short- or medium-term among surgical patients and to study the potential genetic association among these two entities. We searched electronic databases for reserch studies to evaluate the association of APOE4 with postoperative delirium (POD) or short- and medium term postoperative cognitive dysfunction (POCD). Twenty-two trials (16 prospective and six retrospective) with 6734 patients were included. APOE4 alleles was shown significantly associated with POCD within 1 week (odds ratio, OR, 1.89, 95% confidence interval, CI, 1.36 to 2.6278, p < 0.01) in the random-effects model. A significant association was also noted between APOE4 and POCD in medium-term, 1-3 months, after surgery (OR: 1.67, 95% CI: 1.003-2.839, p = 0.049). However, APOE4 was not significantly associated with POCD 1 year after surgery (OR: 0.98, 95% CI: 0.57-1.70, p = 0.9449) and POD (OR: 1.28, 95% CI: 0.85-1.91, p = 0.23). In conclusion, APOE4 alleles was genetically associated with short- and medium-term postoperative neurological dysfunction and future screening or preventive strategies derived is highly potential to improve outcomes.
MeSH term(s)	Humans ; Postoperative Cognitive Complications/diagnosis ; Apolipoprotein E4/genetics ; Delirium/diagnosis ; Retrospective Studies ; Alleles ; Prospective Studies ; Cognitive Dysfunction/genetics ; Postoperative Complications/prevention & control
Chemical Substances	Apolipoprotein E4
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0282214
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Article ; Online: Annotation of 1350 Common Genetic Variants of the 19 ALDH Multigene Family from Global Human Genome Aggregation Database (gnomAD).

Chen, Che-Hong / Kraemer, Benjamin R / Lee, Lucia / Mochly-Rosen, Daria

Biomolecules

2021 Volume 11, Issue 10

Abstract: Human aldehyde dehydrogenase (ALDH) is a multigene family with 19 functional members encoding a class of diverse but important enzymes for detoxification or biotransformation of different endogenous and exogenous aldehyde substrates. Genetic mutations in ...

Abstract	Human aldehyde dehydrogenase (ALDH) is a multigene family with 19 functional members encoding a class of diverse but important enzymes for detoxification or biotransformation of different endogenous and exogenous aldehyde substrates. Genetic mutations in the ALDH genes can cause the accumulation of toxic aldehydes and abnormal carbonyl metabolism and serious human pathologies. However, the physiological functions and substrate specificity of many ALDH genes are still unknown. Although many genetic variants of the ALDH gene family exist in human populations, their phenotype or clinical consequences have not been determined. Using the most comprehensive global human Genome Aggregation Database, gnomAD, we annotated here 1350 common variants in the 19 ALDH genes. These 1350 common variants represent all known genetic polymorphisms with a variant allele frequency of ≥0.1% (or an expected occurrence of ≥1 carrier per 500 individuals) in any of the seven major ethnic groups recorded by gnomAD. We detailed 13 types of DNA sequence variants, their genomic positions, SNP ID numbers, and allele frequencies among the seven major ethnic groups worldwide for each of the 19 ALDH genes. For the 313 missense variants identified in the gnomAD, we used two software algorithms, Polymorphism Phenotyping (PolyPhen) and Sorting Intolerant From Tolerant (SIFT), to predict the consequences of the variants on the structure and function of the enzyme. Finally, gene constraint analysis was used to predict how well genetic mutations were tolerated by selection forces for each of the ALDH genes in humans. Based on the ratio of observed and expected variant numbers in gnomAD, the three ALDH1A gene members, ALDH1A1, ALDH1A2, and ALDH1A3, appeared to have the lowest tolerance for loss-of-function mutations as compared to the other ALDH genes (# observed/# expected ratio 0.15-0.26). These analyses suggest that the ALDH1A1, ALDH1A2, and ALDH1A3 enzymes may serve a more essential function as compared with the other ALDH enzymes; functional loss mutations are much less common in healthy human populations than expected. This informatic analysis may assist the research community in determining the physiological function of ALDH isozymes and associate common variants with clinical phenotypes.
MeSH term(s)	Aldehyde Dehydrogenase/classification ; Aldehyde Dehydrogenase/genetics ; Databases, Genetic ; Gene Frequency/genetics ; Genome, Human/genetics ; Genomics ; Humans ; Molecular Sequence Annotation ; Multigene Family/genetics ; Polymorphism, Genetic/genetics
Chemical Substances	Aldehyde Dehydrogenase (EC 1.2.1.3)
Language	English
Publishing date	2021-09-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11101423
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Article ; Online: The Role of Alcohol, LPS Toxicity, and ALDH2 in Dental Bony Defects.

Tsai, Hsiao-Cheng / Chen, Che-Hong / Mochly-Rosen, Daria / Li, Yi-Chen Ethan / Chen, Min-Huey

Biomolecules

2021 Volume 11, Issue 5

Abstract: It is estimated that 560 million people carry an East Asian-specific ALDH2*2 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH2*2 ... ...

Abstract	It is estimated that 560 million people carry an East Asian-specific ALDH22 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH22 mutation in conjunction with periodontal
MeSH term(s)	Alcohol Drinking/adverse effects ; Alcohol Drinking/genetics ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; Aldehyde Dehydrogenase, Mitochondrial/metabolism ; Animals ; Bone Regeneration/drug effects ; Bone Regeneration/genetics ; Calcification, Physiologic/drug effects ; Cell Line ; Cell Proliferation/drug effects ; Humans ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Periodontitis/genetics ; Periodontitis/physiopathology ; Porphyromonas gingivalis/physiology ; X-Ray Microtomography
Chemical Substances	Lipopolysaccharides ; Aldehyde Dehydrogenase, Mitochondrial (EC 1.2.1.3)
Language	English
Publishing date	2021-04-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom11050651
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