Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism

@article{Bosron1986GeneticPO,
  title={Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism},
  author={William F. Bosron and Ting-kai Li},
  journal={Hepatology},
  year={1986},
  volume={6}
}
It is now widely accepted that the various pharmacologic and addictive consequences of alcohol consumption are related to the tissue concentration of ethanol or its metabolic products. The oxidative metabolism of ethanol in liver is principally catalyzed by alcohol dehydrogenase and aldehyde dehydrogenase. Both of these enzymes exist in multiple molecular forms, and genetic models have been proposed to account for the multiplicity of isoenzymes. Alcohol dehydrogenase subunits are encoded at… 
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564 Citations

Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease.

Genetic Polymorphism and Properties of Human Alcohol and Aldehyde Dehydrogenases: Implications for Ethanol Metabolism and Toxicity

Some of the recent advances about ethanol metabolism and acetaldehyde toxicity in various tissues and organs of individuals with genetically different forms of ADH and ALDH isoenzymes are summarized.

Alcohol-metabolizing enzyme polymorphisms and alcoholism in Japan.

Genetic polymorphisms of the ADH and ALDH genes, but not of the P450IIE1 gene, influence the risk of developing alcoholism in Japanese.

Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol‐related end‐organ damage

Compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol‐related cirrhosis and chronic pancreatitis are compared with 79 local healthy control subjects to study genetically determined differences in ethanol metabolism.

Association of polymorphism in the alcohol dehydrogenase 2 gene with alcohol‐related organ injuries, especially liver cirrhosis

The role of polymorphisms at the ADH2 loci in genetic predisposition to alcoholism and alcohol‐related organ injury, especially alcoholic cirrhosis is reviewed.

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

The strongest correlations found to date have been those between the ALDH2*2 allele and cancers of the oro-pharynx and oesophagus, and it will be important to replicate other interesting associations between these variants and other cancers and heart disease, and to determine the biochemical mechanisms underlying the associations.

Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men.

The genotypes of the ADH2, ADH3, and ALDH2 loci of alcoholic and nonalcoholic Chinese men living in Taiwan are determined using leukocyte DNA amplified by the PCR and allele-specific oligonucleotides, suggesting that genetic variation in both ADH and AL DH, by modulating the rate of metabolism of ethanol and acetaldehyde, influences drinking behavior and the risk of developing alcoholism.

Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai

The results fit the proposed hypothesis for the development of alcoholism, i.e., drinking behavior is greatly influenced by the individual's gentoypes of alcohol-metabolizing enzymes, and the risk of becoming alcoholic is proportionate with the ethanol consumption of the individual.

Influence of Genetic Variations of Ethanol‐Metabolizing Enzymes on Phenotypes of Alcohol‐Related Disorders

Examining the influence of genetic variations of these enzymes on alcohol‐related disorders in the Japanese revealed that the less active allele of the ADH2 gene (ADH2*1) is associated with an increased risk for alcohol dependence, alcohol‐induced persistent amnestic disorder, alcohol withdrawal syndrome, and cancer of the upper GI tract.

Genetic Associations of Alcohol and Aldehyde Dehydrogenase With Alcohol Dependence and Their Mechanisms of Action

  • T. Wall
  • Medicine
    Therapeutic drug monitoring
  • 2005
Data are consistent with the hypothesis that elevations in acetaldehyde, increased sensitivity to alcohol, and lower levels of drinking reflect the mechanism by which the ALDH2*2 allele reduces risk for alcohol dependence.
...

References

SHOWING 1-10 OF 68 REFERENCES

Heterogeneity and polymorphism of human-liver alcohol dehydrogenase.

Only little is known about the physiological function of ADH at these localizations, but Vitamin A and steroids are known to represent substrates of some ADH isoenzymes, suggesting that the enzyme may fulfill specific tasks at these unexpected localizations.

New molecular forms of human liver alcohol dehydrogenase: isolation and characterization of ADHIndianapolis.

  • W. BosronT. LiB. Vallee
  • Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1980
Based upon the electrophoretic pattern of livers containing ADHIndianapolis and the mobility of the three isolated molecular forms, ADH Indianapolis may be the result of polymorphism at the ADH2 gene locus, which codes for the beta subunit.

Alcohol dehydrogenase isozymes in adult human stomach and liver: evidence for activity of the ADH3 locus

It appears that most of theADH activity in adult stomach is derived from the ADH, locus, and certain isozymes which had previously been observed in adult liver, but which at that time could not be easily accounted for in terms of the three-locus hypothesis are considered.

Enzymatic and structural differences between usual and atypical human liver alcohol dehydrogenases.

Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication.

A high incidence in the Japanese of the unusual phenotype of ALDH, which lacks in the low Km isozyme, suggests that the initial intoxicating symptoms after alcohol drinking in these subjects might be due to delayed oxidation of acetaldehyde rather than its higher-than-normal production by typical or atypical ADH.

Isolation of pi-alcohol dehydrogenase of human liver: is it a determinant of alcoholism?

The isolation of human II-ADH advances efforts to recognize and understand biochemical mechanisms that may be biological determinants of alcoholism and alcohol-related disease states, now generally approached and managed largely as psychosocial disorders.

Relationship between kinetics of liver alcohol dehydrogenase and alcohol metabolism

Genetic and developmental regulation of mouse liver alcohol dehydrogenase.

Human liver alcohol dehydrogenase

Determination of the amino acid sequence of the β1 subunit from the class I (pyrazole-sensitive) human liver alcohol dehydrogenase isoenzyme β1β1 revealed a 373-residue structure, compatible with known differences in composition, ultraviolet absorbance, electrophoretic mobility and catalytic properties between the horse and human enzymes.

Biology of disease. Alcoholism and aldehydism: new biomedical concepts.

The hypothesis is put forward that the individual and racial differences in alcohol metabolism are based on the genetically determined variability of the participating enzymes, alcohol dehydrogenase and aldehyde dehydration, which could serve as a biologic marker for high risk drinking.
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