Home LiteratureArticle Details
PMID: 2562960 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant.

The Journal of clinical investigation ·Vol. 83 ·No. 1 ·1989-01-00 ·Pages 314-6

Crabb DW, Edenberg HJ, Bosron WF, Li TK

Abstract

Many Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity responsible for the oxidation of acetaldehyde produced during ethanol metabolism. These individuals suffer the alcohol-flush reaction when they drink alcoholic beverages. The alcohol-flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption. The subunit of this homotetrameric enzyme was sequenced and the abnormality in the inactive enzyme shown to be a substitution of lysine for glutamate at position 487. We have used the polymerase chain reaction to determine the genotypes of 24 livers from Japanese individuals. Correlating genotype with phenotype leads to the conclusion that the allele (ALDH2(2)) encoding the abnormal subunit is dominant.

MeSH Terms
Aldehyde Dehydrogenase/deficiency,genetics Alleles Ethanol/metabolism Gene Amplification Genotype Glutamates Glutamic Acid Humans Liver/enzymology Lysine Phenotype
Chemicals
Glutamates Ethanol Glutamic Acid Aldehyde Dehydrogenase Lysine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Crabb D W
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Edenberg H J
Bosron W F
Li T K
References (31)
31 references, click to expand
  1. Genetic studies on alcohol-metabolizing enzymes: detection of isozymes in human hair roots.
    Enzyme. 1980;25(4):281-6 PMID: 6998700
  2. Inheritance of alcohol abuse. Cross-fostering analysis of adopted men.
    Arch Gen Psychiatry. 1981 Aug;38(8):861-8 PMID: 7259422
  3. Possible protective role against alcoholism for aldehyde dehydrogenase isozyme deficiency in Japan.
    Lancet. 1982 Oct 9;2(8302):827 PMID: 6126701
  4. Familial resemblances in flushing following alcohol use.
    Behav Genet. 1982 May;12(3):349-52 PMID: 7126112
  5. Structural mutation in a major human aldehyde dehydrogenase gene results in loss of enzyme activity.
    Am J Hum Genet. 1982 Nov;34(6):837-41 PMID: 7180842
  6. Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers.
    J Biol Chem. 1983 May 25;258(10):6282-7 PMID: 6189823
  7. Aldehyde dehydrogenase isozyme variation and alcoholism in Japan.
    Pharmacol Biochem Behav. 1983;18 Suppl 1:151-3 PMID: 6634831
  8. Low Km ALDH isozyme and alcoholic liver injury.
    Pharmacol Biochem Behav. 1983;18 Suppl 1:425-8 PMID: 6634852
  9. Determination of genotypes of human aldehyde dehydrogenase ALDH2 locus.
    Am J Hum Genet. 1983 Nov;35(6):1107-16 PMID: 6650498
  10. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals.
    Proc Natl Acad Sci U S A. 1984 Jan;81(1):258-61 PMID: 6582480
  11. Human aldehyde dehydrogenase: catalytic activity in oriental liver.
    Biochem Biophys Res Commun. 1984 Jan 13;118(1):97-102 PMID: 6696771
  12. Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics.
    Alcohol. 1985 May-Jun;2(3):391-2 PMID: 4026955
  13. Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations.
    Eur J Biochem. 1985 Nov 15;153(1):13-28 PMID: 4065146
  14. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia.
    Science. 1985 Dec 20;230(4732):1350-4 PMID: 2999980
  15. Aldehyde dehydrogenase polymorphism in North American, South American, and Mexican Indian populations.
    Am J Hum Genet. 1986 Mar;38(3):395-9 PMID: 3953578
  16. Chromosomal assignment of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2.
    Am J Hum Genet. 1986 May;38(5):641-8 PMID: 3013004
  17. Neurogenetic adaptive mechanisms in alcoholism.
    Science. 1987 Apr 24;236(4800):410-6 PMID: 2882604
  18. Purification of human liver aldehyde dehydrogenase by high-performance liquid chromatography and identification of isoenzymes by immunoblotting.
    Alcohol Clin Exp Res. 1987 Feb;11(1):60-5 PMID: 3551665
  19. Polymorphism of aldehyde dehydrogenase and alcohol sensitivity.
    Enzyme. 1987;37(1-2):29-44 PMID: 3106030
  20. Direct detection of usual and atypical alleles on the human aldehyde dehydrogenase-2 (ALDH2) locus.
    Am J Hum Genet. 1987 Dec;41(6):996-1001 PMID: 3687946
  21. Genomic structure of the human mitochondrial aldehyde dehydrogenase gene.
    Genomics. 1988 Jan;2(1):57-65 PMID: 2838413
  22. Human liver aldehyde dehydrogenase in Chinese and Asiatic Indians: gene deletion and its possible implications in alcohol metabolism.
    Biochem Genet. 1981 Feb;19(1-2):107-14 PMID: 7225089
  23. Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification.
    Genomics. 1988 Apr;2(3):209-14 PMID: 3397059
  24. Alcohol and aldehyde dehydrogenase isoenzymes in Sioux North American Indians.
    Alcohol Clin Exp Res. 1988 Jun;12(3):454-5 PMID: 3044179
  25. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  26. Human liver alcohol dehydrogenase isoenzyme variations. Improved separation methods using prolonged high voltage starch-gel electrophoresis and isoelectric focusing.
    Hum Genet. 1978 Jan 19;40(2):215-20 PMID: 624549
  27. Some genetic aspects of alcoholism and criminality. A population of adoptees.
    Arch Gen Psychiatry. 1978 Mar;35(3):269-76 PMID: 727885
  28. Relationship between facial flushing and blood acetaldehyde levels after alcohol intake.
    Pharmacol Biochem Behav. 1979 Feb;10(2):303-11 PMID: 450943
  29. Racial differences in alcohol sensitivity: a new hypothesis.
    Hum Genet. 1979 Oct 2;51(3):331-4 PMID: 511165
  30. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication.
    Am J Hum Genet. 1980 Jan;32(1):8-15 PMID: 6987864
  31. Aldehyde dehydrogenase deficiency as cause of facial flushing reaction to alcohol in Japanese.
    Lancet. 1981 Oct 31;2(8253):982 PMID: 6117742
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI113875
Published
1989-01-00
Pages
314-6
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC303676
Subset
IM
Grants
NIAAA NIH HHS · AA-00081 · United States
NIAAA NIH HHS · AA-06434 · United States
NIAAA NIH HHS · P50 AA-07611 · United States
Databases
GENBANK
J03043, M20455
External Links
PubMed source DOI: 10.1172/JCI113875 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2