Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

Quertemont, Étienne

doi:10.1038/sj.mp.4001497

Cited by 150 publications

(100 citation statements)

References 175 publications

(229 reference statements)

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“…The ALDH2*2 allele is common in East Asian populations, in whom it has a well-established protective effect associated with about a 10-fold reduction in risk of alcoholism. 82 The protective effect is thought to be a direct consequence of the flushing reaction and associated nausea, drowsiness and headache that discourages drinking. In a recent meta-analysis, 83 researchers found clear evidence of a correlation between ALDH2 genotype and alcohol exposure (alcohol exposure being considered an environmental risk factor for cancer in much the same way that some psychiatrists view cannabis use as an environmental risk factor for schizophrenia).…”

Section: Genotype-environment Associations: Challenges In Identifyingmentioning

confidence: 99%

Gene–environment correlations: a review of the evidence and implications for prevention of mental illness

2007

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Family studies have demonstrated genetic influences on environmental exposure: the phenomenon of gene-environment correlation (rGE). A few molecular genetic studies have confirmed the results, but the identification of rGE in studies that measure genes and environments faces several challenges. Using examples from studies in psychology and psychiatry, we integrate the behavioral and molecular genetic literatures on rGE, describe challenges in identifying rGE and discuss the implications of molecular genetic findings of rGE for future research on gene-environment interplay and for attempts to prevent disease by reducing environmental risk exposure. Genes affect environments indirectly, via behavior and personality characteristics. Associations between individual genetic variants and behaviors are typically small in magnitude, and downstream effects on environmental risk are further attenuated by behavioral mediation. Genotype-environment associations are most likely to be detected when the environment is behaviorally modifiable and highly specified and a plausible mechanism links gene and behavior. rGEs play an important causal role in psychiatric illness. Although research efforts should concentrate on elucidating the genetic underpinnings of behavior rather than the environment itself, the identification of rGE may suggest targets for environmental intervention even in highly heritable disease. Prevention efforts must address the possibility of confounding between rGE and gene-environment interaction (G Â E).

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Section: Genotype-environment Associations: Challenges In Identifyingmentioning

confidence: 99%

Gene–environment correlations: a review of the evidence and implications for prevention of mental illness

2007

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“…Since acetaldehyde is much more toxic than alcohol, it is associated with a larger number of the metabolic abnormalities in liver disease induced by alcohol. 9,10) Under normal conditions, acetaldehyde is rapidly converted to acetate by ADH, and therefore very low level of acetaldehyde should remain in the liver tissue or blood. ALDH also plays an important role in the elimination of acetaldehyde through oxidative reactions.…”

mentioning

confidence: 99%

Glycoprotein Isolated from Acanthopanax senticosus Protects against Hepatotoxicity Induced by Acute and Chronic Alcohol Treatment

Choi

Yoon²,

Kang

et al. 2006

Biological & Pharmaceutical Bulletin

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Acanthopanax senticosus (A. senticosus) is a common Asian herb known as "Siberian Ginseng" or "Eleutherococcus senticosus" 1) and used for rheumatism and prophylaxis of various diseases including chronic bronchitis, hypertension, and ischemia. The herb has also been known to effectively relieve stress or fatigue, and symptoms associated with diabetes, neuralgia, and cancer. 2,3) Today this oriental herb is called "adatogen" in the U.S.4) The major active components of A. senticosus are acanthoside, eleutheroside, chiisanoside, senticoside, triterpenic saponin, syringin, flavone, vitamin, minerals, b-sitosterol, sesamine and savinine. 4,5) Each chemical compound is known to produce diverse biological activities. In Korea, the extract of the A. senticosus plant is used a component in traditional herbal Korean medicine, and is available as a functional beverage commercially marketed for reducing liver damage and accelerating alcohol detoxification. The efficacy of A. senticosus in animal modes and the mechanisms underlying the aforementioned physiological properties involved in alcohol metabolism is unclear, and is therefore the purpose of this investigation.As much as 80-90% of ingested alcohol is metabolized in the liver, where alcohol is oxidized to acetadehyde. [6][7][8] The process is catalyzed by 3 different enzymes: alcohol dehydrogenase (ADH), microsomal ethanol metabolizing system (MEOS), and acetaldehyde dehydrogenase (ALDH). Since acetaldehyde is much more toxic than alcohol, it is associated with a larger number of the metabolic abnormalities in liver disease induced by alcohol.9,10) Under normal conditions, acetaldehyde is rapidly converted to acetate by ADH, and therefore very low level of acetaldehyde should remain in the liver tissue or blood. ALDH also plays an important role in the elimination of acetaldehyde through oxidative reactions.11) Therefore, the severity of liver diseases can be proportional to reductions in ADH or ALDH activities. 2,12) Development of fatty liver and hyperlipidemia frequently occurs in chronic alcoholics; mainly because ethanol becomes a preferred fuel for the liver and displaces fat as a source of energy, which results in fat accumulation. Furthermore, the redox state secondary to ethanol oxidation is altered, promotings lipogenesis through increasing a-glycerophosphate and acylglycerols. The depressed oxidative capacity of mitochondria caused by chronic alcohol also contributes to fatty liver. Increasing fat accumulations in the liver can also stimulate secretion of lipoproteins into the bloodstream, facilitating the development of hyperlipidemia. Acetyl CoA carboxylase (ACC) is an enzyme that catalyzes the first step in fatty acids biosynthesis and is a rate-limiting enzyme in lipogenesis.5,13) Moreover, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphoglucuronic acid dehydrogenase (6-PGDH) are also involved in lipogenesis by supplying NADPH, an essential cofactor for fatty acids and cholesterol biosynthesis. Alcohol has also been suggested ...

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“…Recently, in our review we suggested indirect mechanisms by which alcohol disrupts the EMPS . However, based on increasing evidences (Deitrich et al, 2006;Wick et al, 1998;Quertemont 2004;Buhler et al, 1983), a direct disruption might also be possible, especially, if we consider the possibility that receptors of neuromediators might have "alcohol pockets-receptors". It is reported that glycine and GABAA receptors may harbor specific pockets for alcohol .…”

Section: Pathways Of Alcohol's Action On the Error Monitoring And Promentioning

confidence: 99%

“…Indirect effect of alcohol on the processing capacity of the basal ganglia by affecting other brain areas connected to the basal ganglia; c. Direct effect on neuromediators that modulate the processing of information in the basal ganglia and/or associated brain pathways; d. Action of alcohol metabolites (acetaldehyde; acetate; protein, lipid, enzyme & DNA adducts of alcohol) on the processing of information in the basal ganglia and/or associated brain pathways. The brain might contain alcohol metabolizing enzymes such as ADH-1, ADH-2, ADH-3 (might play little or no role), CYP P4502E1 (Quertemont 2004;Buhler et al, 1983), although there might be a huge genetic variance. It important to note that injection of acetate into the brain causes significant decrease in motor function (Deitrich et al, 2006).…”

Section: Pathways Of Alcohol's Action On the Error Monitoring And Promentioning

confidence: 99%

Basal Ganglia and the Error Monitoring and Processing System: How Alcohol Modulates the Error Monitoring and Processing Capacity of the Basal Ganglia

Welcome¹,

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2013

Basal Ganglia - An Integrative View

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Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

Cited by 150 publications

References 175 publications

Gene–environment correlations: a review of the evidence and implications for prevention of mental illness

Gene–environment correlations: a review of the evidence and implications for prevention of mental illness

Glycoprotein Isolated from Acanthopanax senticosus Protects against Hepatotoxicity Induced by Acute and Chronic Alcohol Treatment

Basal Ganglia and the Error Monitoring and Processing System: How Alcohol Modulates the Error Monitoring and Processing Capacity of the Basal Ganglia

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