Cited by 159Alcohol Consumption and Health EffectsSubstance Abuse Treatment and OutcomesGenetic Associations and Epidemiology

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Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians

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Li, Dawei, Zhao, Hongyu, Gelernter, Joel·2012·Human Genetics

DOI 10.1007/s00439-011-1116-4PMC PMC3548401

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Abstract

Alcohol is oxidized to acetaldehyde, which in turn is oxidized to acetate. The aldehyde dehydrogenase 2 gene (ALDH2) is the most important gene responsible for acetaldehyde metabolism. Individuals heterozygous or homozygous for the lys (A or *2) allele at the single nucleotide polymorphism (SNP) glu504lys (rs671) of ALDH2 have greatly reduced ability to metabolize acetaldehyde, which greatly decreases their risk for alcohol dependence (AD). Case-control studies have shown association between this SNP and alcohol dependence as well as alcohol-induced liver disease. However, some studies have produced insignificant results. Using cumulative data from the past 20 years predominately from Asian populations (from both English and Chinese publications), this meta-analysis sought to examine and update whether the aggregate data provide new evidence of statistical significance for the proposed association. Our results (9,678 cases and 7,331 controls from 53 studies) support a strong association of alcohol abuse and dependence, with allelic P value of 3 × 10(-56) and OR of 0.23 (0.2, 0.28) under the random effects model. The dominant model (lys-lys + lys-glu vs. glu-glu) also showed strong association with P value of 1 × 10(-44) and OR of 0.22 (0.18, 0.27). When stricter criteria and various sub-group analyses were applied, the association remained strong (for example, OR = 0.23 (0.18, 0.3) and P = 2 × 10(-28) for the alcoholic patients with alcoholic liver disease, cirrhosis, or pancreatitis). These findings provide confirmation of the involvement of the human ALDH2 gene in the pathogenesis of AD as well as alcohol-induced medical illnesses in East-Asians.

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Authors: Li, D., Zhao, H., & Gelernter, J.
Affiliations: Yale University (US)
Corresponding author: Li, Dawei
ORCID: Li, Dawei
Zhao, Hongyu
Gelernter, Joel
Venue: Human Genetics
Publisher: Springer Science and Business Media LLC
Published: 2011-11-20
Volume: 131
Issue: 5
Pages: 725-737
ISSN: 0018-7348 (ISSN-L)
0340-6717
1432-1203
DOI: 10.1007/s00439-011-1116-4
PMC: PMC3548401
OpenAlex: W2002696968
Cited by: 158
References: 102
Citations by year: 2026: 6 · 2025: 7 · 2024: 11 · 2023: 5 · 2022: 17 · 2021: 11 · 2020: 11 · 2019: 16 · 2018: 11 · 2017: 12 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 13 · 2012: 6
FWCI: 6.98
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Human Genetics (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism (AA11330, AA 12870, AA017535, R01AA017535, R01AA011330, P50AA012870)
National Institute on Drug Abuse (DA-12849, DA 12690, R01DA012690, R01DA012849)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: ALDH2, rs671, alcoholism, alcoholic liver disease, alcoholic cirrhosis, alcoholic pancreatitis, acetaldehyde metabolism, genetic susceptibility, East Asian populations
MeSH terms: Aldehyde Dehydrogenase, Mitochondrial, Alcohol Drinking, Alcoholism, Aldehyde Dehydrogenase, Alleles, Humans, Liver Cirrhosis, Liver Diseases, Alcoholic, Pancreatitis, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Asian People, Disease Resistance

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Strong protective effect of the aldehyde dehydrogenase gene (ALDH2) 504lys (*2) allele against alcoholism and alcohol-induced medical diseases in Asians

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